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2,084 results on '"McLean, Catriona A."'

1. Early onset diagnosis in Alzheimers disease patients via amyloid-β oligomers-sensing probe in cerebrospinal fluid.

Author

An, Jusung, Kim, Kyeonghwan, Lim, Ho, Kim, Hye, Shin, Jinwoo, Park, InWook, Cho, Illhwan, Kim, Hyeong, McLean, Catriona, Choi, Kyu, Kim, YoungSoo, Lee, Kun, Kim, Jong, and Kim, Sunghoon

Subjects
Humans, Alzheimer Disease, Amyloid beta-Peptides, Cognitive Dysfunction, Biomarkers, Amyloidogenic Proteins, tau Proteins, Peptide Fragments
Abstract

Amyloid-β (Aβ) oligomers are implicated in the onset of Alzheimers disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aβ oligomers by finely tailoring the hydrophobicity of the biannulate donor motifs in donor-π-acceptor structure. Q-OB shows a great sensing potency in dynamically monitoring oligomerization of Aβ during amyloid fibrillogenesis in vitro. In addition, we applied this strategy to fluorometrically analyze Aβ self-assembly kinetics in the cerebrospinal fluids (CSF) of AD patients. The fluorescence intensity of Q-OB in AD patients CSF revealed a marked change of log (I/I0) value of 0.34 ± 0.13 (cognitive normal), 0.15 ± 0.12 (mild cognitive impairment), and 0.14 ± 0.10 (AD dementia), guiding to distinguish a state of AD continuum for early diagnosis of AD. These studies demonstrate the potential of our approach can expand the currently available preclinical diagnostic platform for the early stages of AD, aiding in the disruption of pathological progression and the development of appropriate treatment strategies.

Published
2024

2. Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S, Dombroski, Beth A, Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C, Dopper, Elise, Ghetti, Bernardino F, Newell, Kathy L, Troakes, Claire, de Yébenes, Justo G, Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H, Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G, Serrano, Geidy E, Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A, Galasko, Douglas, Boxer, Adam L, Miller, Bruce L, Seeley, Willian W, Van Deerlin, Vivanna M, Lee, Edward B, White, Charles L, Morris, Huw, de Silva, Rohan, Crary, John F, Goate, Alison M, Friedman, Jeffrey S, Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C, Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W, Höglinger, Günter U, Schellenberg, Gerard D, Geschwind, Daniel H, and Lee, Wan-Ping

Subjects
Biological Sciences, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Rare Diseases, Neurosciences, Dementia, Human Genome, Brain Disorders, Biotechnology, Aging, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease, 2.1 Biological and endogenous factors, Neurological, Progressive Supranuclear Palsy, Whole-Genome Sequencing, Genome-Wide Association Study, Structural Variants, Apolipoprotein E, P. S. P. genetics study group, Humans, Supranuclear Palsy, Progressive, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Whole Genome Sequencing, Clinical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).MethodIn this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed.ResultsOur analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP.ConclusionsThrough WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

Published
2024

3. A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry

Author

Cortese, Andrea, Beecroft, Sarah J., Facchini, Stefano, Curro, Riccardo, Cabrera-Serrano, Macarena, Stevanovski, Igor, Chintalaphani, Sanjog R., Gamaarachchi, Hasindu, Weisburd, Ben, Folland, Chiara, Monahan, Gavin, Scriba, Carolin K., Dofash, Lein, Johari, Mridul, Grosz, Bianca R., Ellis, Melina, Fearnley, Liam G., Tankard, Rick, Read, Justin, Merve, Ashirwad, Dominik, Natalia, Vegezzi, Elisa, Schnekenberg, Ricardo P., Fernandez-Eulate, Gorka, Masingue, Marion, Giovannini, Diane, Delatycki, Martin B., Storey, Elsdon, Gardner, Mac, Amor, David J., Nicholson, Garth, Vucic, Steve, Henderson, Robert D., Robertson, Thomas, Dyke, Jason, Fabian, Vicki, Mastaglia, Frank, Davis, Mark R., Kennerson, Marina, Quinlivan, Ros, Hammans, Simon, Tucci, Arianna, Bahlo, Melanie, McLean, Catriona A., Laing, Nigel G., Stojkovic, Tanya, Houlden, Henry, Hanna, Michael G., Deveson, Ira W., Lockhart, Paul J., Lamont, Phillipa J., Fahey, Michael C., Bugiardini, Enrico, and Ravenscroft, Gianina

Published
2024
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4. Author Correction: A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry

Author

Cortese, Andrea, Beecroft, Sarah J., Facchini, Stefano, Curro, Riccardo, Cabrera-Serrano, Macarena, Stevanovski, Igor, Chintalaphani, Sanjog R., Gamaarachchi, Hasindu, Weisburd, Ben, Folland, Chiara, Monahan, Gavin, Scriba, Carolin K., Dofash, Lein, Johari, Mridul, Grosz, Bianca R., Ellis, Melina, Fearnley, Liam G., Tankard, Rick, Read, Justin, Merve, Ashirwad, Dominik, Natalia, Vegezzi, Elisa, Schnekenberg, Ricardo P., Fernandez-Eulate, Gorka, Masingue, Marion, Giovannini, Diane, Delatycki, Martin B., Storey, Elsdon, Gardner, Mac, Amor, David J., Nicholson, Garth, Vucic, Steve, Henderson, Robert D., Robertson, Thomas, Dyke, Jason, Fabian, Vicki, Mastaglia, Frank, Davis, Mark R., Kennerson, Marina, Quinlivan, Ros, Hammans, Simon, Tucci, Arianna, Bahlo, Melanie, McLean, Catriona A., Laing, Nigel G., Stojkovic, Tanya, Houlden, Henry, Hanna, Michael G., Deveson, Ira W., Lockhart, Paul J., Lamont, Phillipa J., Fahey, Michael C., Bugiardini, Enrico, and Ravenscroft, Gianina

Published
2024
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5. Correction: Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S., Dombroski, Beth A., Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C., Dopper, Elise, Ghetti, Bernardino F., Newell, Kathy L., Troakes, Claire, de Yébenes, Justo G., Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H., Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G., Serrano, Geidy E., Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A., Galasko, Douglas, Boxer, Adam L., Miller, Bruce L., Seeley, Willian W., Van Deerlin, Vivanna M., Lee, Edward B., White, III, Charles L., Morris, Huw, de Silva, Rohan, Crary, John F., Goate, Alison M., Friedman, Jeffrey S., Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C., Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W., Höglinger, Günter U., Schellenberg, Gerard D., Geschwind, Daniel H., and Lee, Wan-Ping

Published
2024
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8. Microglial ferroptotic stress causes non-cell autonomous neuronal death

Author

Liddell, Jeffrey R., Hilton, James B. W., Kysenius, Kai, Billings, Jessica L., Nikseresht, Sara, McInnes, Lachlan E., Hare, Dominic J., Paul, Bence, Mercer, Stephen W., Belaidi, Abdel A., Ayton, Scott, Roberts, Blaine R., Beckman, Joseph S., McLean, Catriona A., White, Anthony R., Donnelly, Paul S., Bush, Ashley I., and Crouch, Peter J.

Published
2024
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9. Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.

Author

Hopfner, Franziska, Tietz, Anja, Ruf, Viktoria, Ross, Owen, Koga, Shunsuke, Dickson, Dennis, Aguzzi, Adriano, Attems, Johannes, Beach, Thomas, Beller, Allison, Cheshire, William, van Deerlin, Vivianna, Deuschl, Günther, Duyckaerts, Charles, Ellinghaus, David, Evsyukov, Valentin, Flanagan, Margaret, Franke, Andre, Frosch, Matthew, Gearing, Marla, Gelpi, Ellen, van Gerpen, Jay, Ghetti, Bernardino, Glass, Jonathan, Halliday, Glenda, Helbig, Ingo, Höllerhage, Matthias, Huitinga, Inge, Irwin, David, Keene, Dirk, Kovacs, Gabor, Lee, Edward, Levin, Johannes, Martí, Maria, Mackenzie, Ian, McKeith, Ian, Mclean, Catriona, Mollenhauer, Brit, Neumann, Manuela, Newell, Kathy, Pantelyat, Alex, Pendziwiat, Manuela, Peters, Annette, Molina Porcel, Laura, Rabano, Alberto, Matěj, Radoslav, Rajput, Alex, Rajput, Ali, Reimann, Regina, Scott, William, Selvackadunco, Sashika, Simuni, Tanya, Stadelmann, Christine, Svenningsson, Per, Thomas, Alan, Trenkwalder, Claudia, Troakes, Claire, Trojanowski, John, Uitti, Ryan, White, Charles, Wszolek, Zbigniew, Xie, Tao, Ximelis, Teresa, Yebenes, Justo, Müller, Ulrich, Schellenberg, Gerard, Herms, Jochen, Kuhlenbäumer, Gregor, Höglinger, Günter, Grinberg, Lea, Seeley, William, and Desplats, Paula

Subjects
ZIC1, ZIC4, autopsy-confirmed, genome-wide association study, multiple system atrophy, Autoantibodies, Autopsy, Genome-Wide Association Study, Humans, Multiple System Atrophy, Nerve Tissue Proteins, Olivopontocerebellar Atrophies, Striatonigral Degeneration, Transcription Factors, alpha-Synuclein
Abstract

BACKGROUND: Multiple System Atrophy is a rare neurodegenerative disease with alpha-synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome-wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. OBJECTIVE: Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy-confirmed cases. METHODS: We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). RESULTS: The most strongly disease-associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P-values below 5 × 10-6 , all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). INTERPRETATION: Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4-immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4-mediated vulnerability of neurons in Multiple System Atrophy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

10. Integrated elemental analysis supports targeting copper perturbations as a therapeutic strategy in multiple sclerosis

Author

Hilton, James B.W., Kysenius, Kai, Liddell, Jeffrey R., Mercer, Stephen W., Rautengarten, Carsten, Hare, Dominic J., Buncic, Gojko, Paul, Bence, Murray, Simon S., McLean, Catriona A., Kilpatrick, Trevor J., Beckman, Joseph S., Ayton, Scott, Bush, Ashley I., White, Anthony R., Roberts, Blaine R., Donnelly, Paul S., and Crouch, Peter J.

Published
2024
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12. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Author

Le Voyer, Tom, Parent, Audrey V., Liu, Xian, Cederholm, Axel, Gervais, Adrian, Rosain, Jérémie, Nguyen, Tina, Perez Lorenzo, Malena, Rackaityte, Elze, Rinchai, Darawan, Zhang, Peng, Bizien, Lucy, Hancioglu, Gonca, Ghillani-Dalbin, Pascale, Charuel, Jean-Luc, Philippot, Quentin, Gueye, Mame Sokhna, Maglorius Renkilaraj, Majistor Raj Luxman, Ogishi, Masato, Soudée, Camille, Migaud, Mélanie, Rozenberg, Flore, Momenilandi, Mana, Riller, Quentin, Imberti, Luisa, Delmonte, Ottavia M., Müller, Gabriele, Keller, Baerbel, Orrego, Julio, Franco Gallego, William Alexander, Rubin, Tamar, Emiroglu, Melike, Parvaneh, Nima, Eriksson, Daniel, Aranda-Guillen, Maribel, Berrios, David I., Vong, Linda, Katelaris, Constance H., Mustillo, Peter, Raedler, Johannes, Bohlen, Jonathan, Bengi Celik, Jale, Astudillo, Camila, Winter, Sarah, McLean, Catriona, Guffroy, Aurélien, DeRisi, Joseph L., Yu, David, Miller, Corey, Feng, Yi, Guichard, Audrey, Béziat, Vivien, Bustamante, Jacinta, Pan-Hammarström, Qiang, Zhang, Yu, Rosen, Lindsey B., Holland, Steve M., Bosticardo, Marita, Kenney, Heather, Castagnoli, Riccardo, Slade, Charlotte A., Boztuğ, Kaan, Mahlaoui, Nizar, Latour, Sylvain, Abraham, Roshini S., Lougaris, Vassilios, Hauck, Fabian, Sediva, Anna, Atschekzei, Faranaz, Sogkas, Georgios, Poli, M. Cecilia, Slatter, Mary A., Palterer, Boaz, Keller, Michael D., Pinzon-Charry, Alberto, Sullivan, Anna, Droney, Luke, Suan, Daniel, Wong, Melanie, Kane, Alisa, Hu, Hannah, Ma, Cindy, Grombiříková, Hana, Ciznar, Peter, Dalal, Ilan, Aladjidi, Nathalie, Hie, Miguel, Lazaro, Estibaliz, Franco, Jose, Keles, Sevgi, Malphettes, Marion, Pasquet, Marlene, Maccari, Maria Elena, Meinhardt, Andrea, Ikinciogullari, Aydan, Shahrooei, Mohammad, Celmeli, Fatih, Frosk, Patrick, Goodnow, Christopher C., Gray, Paul E., Belot, Alexandre, Kuehn, Hye Sun, Rosenzweig, Sergio D., Miyara, Makoto, Licciardi, Francesco, Servettaz, Amélie, Barlogis, Vincent, Le Guenno, Guillaume, Herrmann, Vera-Maria, Kuijpers, Taco, Ducoux, Grégoire, Sarrot-Reynauld, Françoise, Schuetz, Catharina, Cunningham-Rundles, Charlotte, Rieux-Laucat, Frédéric, Tangye, Stuart G., Sobacchi, Cristina, Doffinger, Rainer, Warnatz, Klaus, Grimbacher, Bodo, Fieschi, Claire, Berteloot, Laureline, Bryant, Vanessa L., Trouillet Assant, Sophie, Su, Helen, Neven, Benedicte, Abel, Laurent, Zhang, Qian, Boisson, Bertrand, Cobat, Aurélie, Jouanguy, Emmanuelle, Kampe, Olle, Bastard, Paul, Roifman, Chaim M., Landegren, Nils, Notarangelo, Luigi D., Anderson, Mark S., Casanova, Jean-Laurent, and Puel, Anne

Published
2023
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14. Early Melanoma Diagnosis with Sequential Dermoscopic Images

Author

Yu, Zhen, Nguyen, Jennifer, Nguyen, Toan D, Kelly, John, Mclean, Catriona, Bonnington, Paul, Zhang, Lei, Mar, Victoria, and Ge, Zongyuan

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Dermatologists often diagnose or rule out early melanoma by evaluating the follow-up dermoscopic images of skin lesions. However, existing algorithms for early melanoma diagnosis are developed using single time-point images of lesions. Ignoring the temporal, morphological changes of lesions can lead to misdiagnosis in borderline cases. In this study, we propose a framework for automated early melanoma diagnosis using sequential dermoscopic images. To this end, we construct our method in three steps. First, we align sequential dermoscopic images of skin lesions using estimated Euclidean transformations, extract the lesion growth region by computing image differences among the consecutive images, and then propose a spatio-temporal network to capture the dermoscopic changes from aligned lesion images and the corresponding difference images. Finally, we develop an early diagnosis module to compute probability scores of malignancy for lesion images over time. We collected 179 serial dermoscopic imaging data from 122 patients to verify our method. Extensive experiments show that the proposed model outperforms other commonly used sequence models. We also compared the diagnostic results of our model with those of seven experienced dermatologists and five registrars. Our model achieved higher diagnostic accuracy than clinicians (63.69% vs. 54.33%, respectively) and provided an earlier diagnosis of melanoma (60.7% vs. 32.7% of melanoma correctly diagnosed on the first follow-up images). These results demonstrate that our model can be used to identify melanocytic lesions that are at high-risk of malignant transformation earlier in the disease process and thereby redefine what is possible in the early detection of melanoma.

Published
2021
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16. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Warner, Thomas T, Jaunmuktane, Zane, Boeve, Bradley F, Duara, Ranjan, Graff-Radford, Neill R, Josephs, Keith A, Knopman, David S, Koga, Shunsuke, Murray, Melissa E, Lyons, Kelly E, Pahwa, Rajesh, Petersen, Ronald C, Whitwell, Jennifer L, Grinberg, Lea T, Miller, Bruce, Schlereth, Athena, Spina, Salvatore, Grossman, Murray, Irwin, David J, Suh, EunRan, Trojanowski, John Q, Van Deerlin, Vivianna M, Wolk, David A, Connors, Theresa R, Dooley, Patrick M, Oakley, Derek H, Aldecoa, Iban, Balasa, Mircea, Gelpi, Ellen, Borrego-Écija, Sergi, Gascon-Bayarri, Jordi, Sánchez-Valle, Raquel, Sanz-Cartagena, Pilar, Piñol-Ripoll, Gerard, Bigio, Eileen H, Flanagan, Margaret E, Rogalski, Emily J, Weintraub, Sandra, Schneider, Julie A, Peng, Lihua, Zhu, Xiongwei, Chang, Koping, Troncoso, Juan C, Prokop, Stefan, Newell, Kathy L, Jones, Matthew, Richardson, Anna, Roncaroli, Federico, Snowden, Julie, Allinson, Kieren, Singh, Poonam, Serrano, Geidy E, Flowers, Xena E, Goldman, James E, Heaps, Allison C, Leskinen, Sandra P, Black, Sandra E, Masellis, Mario, King, Andrew, Al-Sarraj, Safa, Troakes, Claire, Hodges, John R, Kril, Jillian J, Kwok, John B, Piguet, Olivier, Roeber, Sigrun, Attems, Johannes, Thomas, Alan J, Evers, Bret M., Bieniek, Kevin F, Sieben, Anne A, Cras, Patrick P, De Vil, Bart B, Bird, Thomas, Castellani, Rudolph J, Chaffee, Ann, Franklin, Erin, Haroutunian, Vahram, Jacobsen, Max, Keene, Dirk, Latimer, Caitlin S, Metcalf, Jeff, Perrin, Richard J, Purohit, Dushyant P, Rissman, Robert A, Schantz, Aimee, Walker, Jamie, De Deyn, Peter P, Duyckaerts, Charles, Le Ber, Isabelle, Seilhean, Danielle, Turbant-Leclere, Sabrina, Ervin, John F, Nennesmo, Inger, Riehl, James, Nacmias, Benedetta, Finger, Elizabeth C, Blauwendraat, Cornelis, Nalls, Mike A, Singleton, Andrew B, Vitale, Dan, Cunha, Cristina, Wszolek, Zbigniew K, Valentino, Rebecca R, Scotton, William J, Roemer, Shanu F, Lashley, Tammaryn, Heckman, Michael G, Shoai, Maryam, Martinez-Carrasco, Alejandro, Tamvaka, Nicole, Walton, Ronald L, Baker, Matthew C, Macpherson, Hannah L, Real, Raquel, Soto-Beasley, Alexandra I, Mok, Kin, Revesz, Tamas, Christopher, Elizabeth A, DeTure, Michael, Seeley, William W, Lee, Edward B, Frosch, Matthew P, Molina-Porcel, Laura, Gefen, Tamar, Redding-Ochoa, Javier, Ghetti, Bernardino, Robinson, Andrew C, Kobylecki, Christopher, Rowe, James B, Beach, Thomas G, Teich, Andrew F, Keith, Julia L, Bodi, Istvan, Halliday, Glenda M, Gearing, Marla, Arzberger, Thomas, Morris, Christopher M, White, Charles L, 3rd, Mechawar, Naguib, Boluda, Susana, MacKenzie, Ian R, McLean, Catriona, Cykowski, Matthew D, Wang, Shih-Hsiu J, Graff, Caroline, Nagra, Rashed M, Kovacs, Gabor G, Giaccone, Giorgio, Neumann, Manuela, Ang, Lee-Cyn, Carvalho, Agostinho, Morris, Huw R, Rademakers, Rosa, Hardy, John A, Dickson, Dennis W, Rohrer, Jonathan D, and Ross, Owen A

Published
2024
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17. Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer’s Disease

Author

Hubbard, Evan E, Heil, Lilian R, Merrihew, Gennifer E, Chhatwal, Jasmeer P, Farlow, Martin R, McLean, Catriona A, Ghetti, Bernardino, Newell, Kathy L, Frosch, Matthew P, Bateman, Randall J, Larson, Eric B, Keene, C Dirk, Perrin, Richard J, Montine, Thomas J, MacCoss, Michael J, and Julian, Ryan R

Subjects
Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Aging, Neurodegenerative, Neurosciences, Neurological, Alzheimer Disease, Amyloid beta-Peptides, Autophagy, Brain, Humans, Proteomics, tau Proteins, proteomics, age-related neurodegenerative disease, proteostasis, lysosome, aspartic acid, amyloid, neurofibrillary tangle, amyloid-beta, post-translational modification, hippocampus, Chemical Sciences, Biological Sciences, Biochemistry & Molecular Biology
Abstract

One of the potential benefits of using data-independent acquisition (DIA) proteomics protocols is that information not originally targeted by the study may be present and discovered by subsequent analysis. Herein, we reanalyzed DIA data originally recorded for global proteomic analysis to look for isomerized peptides, which occur as a result of spontaneous chemical modifications to long-lived proteins. Examination of a large set of human brain samples revealed a striking relationship between Alzheimer's disease (AD) status and isomerization of aspartic acid in a peptide from tau. Relative to controls, a surprising increase in isomer abundance was found in both autosomal dominant and sporadic AD samples. To explore potential mechanisms that might account for these observations, quantitative analysis of proteins related to isomerization repair and autophagy was performed. Differences consistent with reduced autophagic flux in AD-related samples relative to controls were found for numerous proteins, including most notably p62, a recognized indicator of autophagic inhibition. These results suggest, but do not conclusively demonstrate, that lower autophagic flux may be strongly associated with loss of function in AD brains. This study illustrates that DIA data may contain unforeseen results of interest and may be particularly useful for pilot studies investigating new research directions. In this case, a promising target for future investigations into the therapy and prevention of AD has been identified.

Published
2022

18. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, Thomas U, Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L, Bolla, Manjeet K, Dennis, Joe, Dunning, Alison M, Lush, Michael, Wang, Qin, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N, Krüger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W, Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G, Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, and McLean, Catriona

Subjects
Human Genome, Cancer, Genetics, Clinical Research, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Biomarkers, Tumor, Breast Neoplasms, Female, Genome-Wide Association Study, Humans, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk, Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, NBCS Collaborators, ABCTB Investigators, kConFab/AOCS Investigators, Receptor, erbB-2, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate

Published
2022

19. Melanoma Diagnosis with Spatio-Temporal Feature Learning on Sequential Dermoscopic Images

Author

Yu, Zhen, Nguyen, Jennifer, Chang, Xiaojun, Kelly, John, Mclean, Catriona, Zhang, Lei, Mar, Victoria, and Ge, Zongyuan

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Existing studies for automated melanoma diagnosis are based on single-time point images of lesions. However, melanocytic lesions de facto are progressively evolving and, moreover, benign lesions can progress into malignant melanoma. Ignoring cross-time morphological changes of lesions thus may lead to misdiagnosis in borderline cases. Based on the fact that dermatologists diagnose ambiguous skin lesions by evaluating the dermoscopic changes over time via follow-up examination, in this study, we propose an automated framework for melanoma diagnosis using sequential dermoscopic images. To capture the spatio-temporal characterization of dermoscopic evolution, we construct our model in a two-stream network architecture which capable of simultaneously learning appearance representations of individual lesions while performing temporal reasoning on both raw pixels difference and abstract features difference. We collect 184 cases of serial dermoscopic image data, which consists of histologically confirmed 92 benign lesions and 92 melanoma lesions, to evaluate the effectiveness of the proposed method. Our model achieved AUC of 74.34%, which is ~8% higher than that of only using single images and ~6% higher than the widely used sequence learning model based on LSTM., Comment: submission of miccai 2020

Published
2020

20. Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

Author

Kapoor, Pooja Middha, Mavaddat, Nasim, Choudhury, Parichoy Pal, Wilcox, Amber N, Lindström, Sara, Behrens, Sabine, Michailidou, Kyriaki, Dennis, Joe, Bolla, Manjeet K, Wang, Qin, Jung, Audrey, Abu-Ful, Zomoroda, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Freeman, Laura E Beane, Becher, Heiko, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chatterjee, Nilanjan, Chenevix-Trench, Georgia, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dai, James Y, Earp, H Shelton, Ekici, Arif B, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Chi, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hatse, Sigrid, Heyworth, Jane, Holleczek, Bernd, Hoover, Robert N, Hopper, John L, Howell, Anthony, Hunter, David J, ABCTB Investigators, kConFab/AOCS Investigators, John, Esther M, Jones, Michael E, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kurian, Allison W, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, MacInnis, Robert J, Martinez, Maria Elena, Maurer, Tabea, McLean, Catriona, Neuhausen, Susan L, Newman, William G, Norman, Aaron, O'Brien, Katie M, Olshan, Andrew F, Olson, Janet E, Olsson, Håkan, and Orr, Nick

Subjects
ABCTB Investigators, kConFab/AOCS Investigators, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Published
2021

21. Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity

Author

Greatorex, Spencer, Kaur, Supreet, Xirouchaki, Chrysovalantou E., Goh, Pei K., Wiede, Florian, Genders, Amanda J., Tran, Melanie, Jia, YaoYao, Raajendiran, Arthe, Brown, Wendy A., McLean, Catriona A., Sadoshima, Junichi, Watt, Matthew J., and Tiganis, Tony

Subjects
Lipids, Cell death, Obesity -- Prevention -- Development and progression, T cells, Inflammation -- Development and progression -- Prevention, Antioxidants, Oxidases, Liver, Proteins, Liver diseases -- Development and progression -- Prevention, Health care industry
Abstract

Nonalcoholic fatty liver disease (NAFLD) is prevalent in the majority of individuals with obesity, but in a subset of these individuals, it progresses to nonalcoholic steatohepatitis (0NASH) and fibrosis. The mechanisms that prevent NASH and fibrosis in the majority of patients with NAFLD remain unclear. Here, we report that NAD(P)H oxidase 4 (NOX4) and nuclear factor erythroid 2-related factor 2 (NFE2L2) were elevated in hepatocytes early in disease progression to prevent NASH and fibrosis. Mitochondria-derived ROS activated NFE2L2 to induce the expression of NOX4, which in turn generated [H.sub.2][O.sub.2] to exacerbate the NFE2L2 antioxidant defense response. The deletion or inhibition of NOX4 in hepatocytes decreased ROS and attenuated antioxidant defense to promote mitochondrial oxidative stress, damage proteins and lipids, diminish insulin signaling, and promote cell death upon oxidant challenge. Hepatocyte NOX4 deletion in high-fat diet-fed obese mice, which otherwise develop steatosis, but not NASH, resulted in hepatic oxidative damage, inflammation, and T cell recruitment to drive NASH and fibrosis, whereas NOX4 overexpression tempered the development of NASH and fibrosis in mice fed a NASH-promoting diet. Thus, mitochondria- and NOX4-derived ROS function in concert to drive a NFE2L2 antioxidant defense response to attenuate oxidative liver damage and progression to NASH and fibrosis in obesity., Introduction Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting 20%-30% of the world's population (1, 2). Although there are strong genetic determinants for disease onset and progression, the [...]

Published
2024
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25. C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy

Author

Cali, Christopher P, Patino, Maribel, Tai, Yee Kit, Ho, Wan Yun, McLean, Catriona A, Morris, Christopher M, Seeley, William W, Miller, Bruce L, Gaig, Carles, Vonsattel, Jean Paul G, White, Charles L, Roeber, Sigrun, Kretzschmar, Hans, Troncoso, Juan C, Troakes, Claire, Gearing, Marla, Ghetti, Bernardino, Van Deerlin, Vivianna M, Lee, Virginia M-Y, Trojanowski, John Q, Mok, Kin Y, Ling, Helen, Dickson, Dennis W, Schellenberg, Gerard D, Ling, Shuo-Chien, and Lee, Edward B

Subjects
Biomedical and Clinical Sciences, Neurosciences, Genetics, Rare Diseases, Acquired Cognitive Impairment, Aging, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), ALS, Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), Dementia, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Autophagy, Basal Ganglia Diseases, Brain, C9orf72 Protein, Frontotemporal Dementia, Humans, Neurodegenerative Diseases, Parkinson Disease, Parkinsonian Disorders, Neurodegeneration, Corticobasal degeneration, C9orf72 repeat expansion, Parkinsonism, Clinical Sciences, Neurology & Neurosurgery
Abstract

Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s-1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). However, whether intermediate expansions also contribute to neurodegenerative disease is not well understood. Several studies have identified intermediate repeats in Parkinson's disease patients, but the association was not found in autopsy-confirmed cases. We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson's but has distinct tau protein pathology. Indeed, intermediate C9orf72 repeats were significantly enriched in autopsy-proven CBD (n = 354 cases, odds ratio = 3.59, p = 0.00024). While large C9orf72 repeat expansions are known to decrease C9orf72 expression, intermediate C9orf72 repeats result in increased C9orf72 expression in human brain tissue and CRISPR/cas9 knockin iPSC-derived neural progenitor cells. In contrast to cases of FTD/ALS with large C9orf72 expansions, CBD with intermediate C9orf72 repeats was not associated with pathologic RNA foci or dipeptide repeat protein aggregates. Knock-in cells with intermediate repeats exhibit numerous changes in gene expression pathways relating to vesicle trafficking and autophagy. Additionally, overexpression of C9orf72 without the repeat expansion leads to defects in autophagy under nutrient starvation conditions. These results raise the possibility that therapeutic strategies to reduce C9orf72 expression may be beneficial for the treatment of CBD.

Published
2019

26. Multisite study of the relationships between antemortem [11C]PIB‐PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

Author

La Joie, Renaud, Ayakta, Nagehan, Seeley, William W, Borys, Ewa, Boxer, Adam L, DeCarli, Charles, Doré, Vincent, Grinberg, Lea T, Huang, Eric, Hwang, Ji‐Hye, Ikonomovic, Milos D, Jack, Clifford, Jagust, William J, Jin, Lee‐Way, Klunk, William E, Kofler, Julia, Lesman‐Segev, Orit H, Lockhart, Samuel N, Lowe, Val J, Masters, Colin L, Mathis, Chester A, McLean, Catriona L, Miller, Bruce L, Mungas, Daniel, O'Neil, James P, Olichney, John M, Parisi, Joseph E, Petersen, Ronald C, Rosen, Howard J, Rowe, Christopher C, Spina, Salvatore, Vemuri, Prashanthi, Villemagne, Victor L, Murray, Melissa E, and Rabinovici, Gil D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Dementia, Bioengineering, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Brain Disorders, Biomedical Imaging, Acquired Cognitive Impairment, Aging, Alzheimer's Disease, Aged, Alzheimer Disease, Aniline Compounds, Autopsy, Female, Humans, Male, Neuropathology, Plaque, Amyloid, Positron-Emission Tomography, Retrospective Studies, Thiazoles, beta-amyloid, Positron emission tomography, Centiloid, CERAD, Thal, Alzheimer's disease neuropathologic changes, Harmonization, Threshold, Pittsburgh compound-B, β-amyloid, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWe sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11C]PIB-positron emission tomography ([11C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification.MethodsFour centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings.ResultsCL values increased with each CERAD neuritic plaque score increment (median -3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET-pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate-to-high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%).DiscussionOur study demonstrated the robustness of a multisite Centiloid [11C]PIB-PET study and established a range of pathology-based CL thresholds.

Published
2019

29. BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting

Author

Scolyer, Richard A., Atkinson, Victoria, Gyorki, David E., Lambie, Duncan, O'Toole, Sandra, Saw, Robyn P.M., Amanuel, Benhur, Angel, Christopher M., Button-Sloan, Alison E., Carlino, Matteo S., Ch'ng, Sydney, Colebatch, Andrew J., Daneshvar, Dariush, Pires da Silva, Inês, Dawson, Tamara, Ferguson, Peter M., Foster-Smith, Erwin, Fox, Stephen B., Gill, Anthony J., Gupta, Ruta, Henderson, Michael A., Hong, Angela M., Howle, Julie R., Jackett, Louise A., James, Craig, Lee, C. Soon, Lochhead, Alistair, Loh, Daphne, McArthur, Grant A., McLean, Catriona A., Menzies, Alexander M., Nieweg, Omgo E., O'Brien, Blake H., Pennington, Thomas E., Potter, Alison J., Prakash, Saurabh, Rawson, Robert V., Read, Rebecca L., Rtshiladze, Michael A., Shannon, Kerwin F., Smithers, B. Mark, Spillane, Andrew J., Stretch, Jonathan R., Thompson, John F., Tucker, Paul, Varey, Alexander H.R., Vilain, Ricardo E., Wood, Benjamin A., and Long, Georgina V.

Published
2022
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31. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Valentino, Rebecca R, primary, Scotton, William J, additional, Roemer, Shanu F, additional, Lashley, Tammaryn, additional, Heckman, Michael G, additional, Shoai, Maryam, additional, Martinez-Carrasco, Alejandro, additional, Tamvaka, Nicole, additional, Walton, Ronald L, additional, Baker, Matthew C, additional, Macpherson, Hannah L, additional, Real, Raquel, additional, Soto-Beasley, Alexandra I, additional, Mok, Kin, additional, Revesz, Tamas, additional, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Seeley, William W, additional, Lee, Edward B, additional, Frosch, Matthew P, additional, Molina-Porcel, Laura, additional, Gefen, Tamar, additional, Redding-Ochoa, Javier, additional, Ghetti, Bernardino, additional, Robinson, Andrew C, additional, Kobylecki, Christopher, additional, Rowe, James B, additional, Beach, Thomas G, additional, Teich, Andrew F, additional, Keith, Julia L, additional, Bodi, Istvan, additional, Halliday, Glenda M, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Morris, Christopher M, additional, White, Charles L, additional, Mechawar, Naguib, additional, Boluda, Susana, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nagra, Rashed M, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Carvalho, Agostinho, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, Ross, Owen A, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, additional, Duara, Ranjan, additional, Graff-Radford, Neill R, additional, Josephs, Keith A, additional, Knopman, David S, additional, Koga, Shunsuke, additional, Murray, Melissa E, additional, Lyons, Kelly E, additional, Pahwa, Rajesh, additional, Petersen, Ronald C, additional, Whitwell, Jennifer L, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, additional, Suh, EunRan, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Wolk, David A, additional, Connors, Theresa R, additional, Dooley, Patrick M, additional, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Schneider, Julie A, additional, Peng, Lihua, additional, Zhu, Xiongwei, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Jones, Matthew, additional, Richardson, Anna, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Singh, Poonam, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Black, Sandra E, additional, Masellis, Mario, additional, King, Andrew, additional, Al-Sarraj, Safa, additional, Troakes, Claire, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Thomas, Alan J, additional, Evers, Bret M., additional, Bieniek, Kevin F, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, Bird, Thomas, additional, Castellani, Rudolph J, additional, Chaffee, Ann, additional, Franklin, Erin, additional, Haroutunian, Vahram, additional, Jacobsen, Max, additional, Keene, Dirk, additional, Latimer, Caitlin S, additional, Metcalf, Jeff, additional, Perrin, Richard J, additional, Purohit, Dushyant P, additional, Rissman, Robert A, additional, Schantz, Aimee, additional, Walker, Jamie, additional, De Deyn, Peter P, additional, Duyckaerts, Charles, additional, Le Ber, Isabelle, additional, Seilhean, Danielle, additional, Turbant-Leclere, Sabrina, additional, Ervin, John F, additional, Nennesmo, Inger, additional, Riehl, James, additional, Nacmias, Benedetta, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, and Wszolek, Zbigniew K, additional

Published
2024
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32. Pathogenic TNNI1 variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease

Author

Donkervoort, Sandra, primary, van de Locht, Martijn, additional, Ronchi, Dario, additional, Reunert, Janine, additional, McLean, Catriona A., additional, Zaki, Maha, additional, Orbach, Rotem, additional, de Winter, Josine M., additional, Conijn, Stefan, additional, Hoomoedt, Daan, additional, Neto, Osorio Lopes Abath, additional, Magri, Francesca, additional, Viaene, Angela N., additional, Foley, A. Reghan, additional, Gorokhova, Svetlana, additional, Bolduc, Véronique, additional, Hu, Ying, additional, Acquaye, Nicole, additional, Napoli, Laura, additional, Park, Julien H., additional, Immadisetty, Kalyan, additional, Miles, Lee B., additional, Essawi, Mona, additional, McModie, Salar, additional, Ferreira, Leonardo F., additional, Zanotti, Simona, additional, Neuhaus, Sarah B., additional, Medne, Livija, additional, ElBagoury, Nagham, additional, Johnson, Kory R., additional, Zhang, Yong, additional, Laing, Nigel G., additional, Davis, Mark R., additional, Bryson-Richardson, Robert J., additional, Hwee, Darren T., additional, Hartman, James J., additional, Malik, Fady I., additional, Kekenes-Huskey, Peter M., additional, Comi, Giacomo Pietro, additional, Sharaf-Eldin, Wessam, additional, Marquardt, Thorsten, additional, Ravenscroft, Gianina, additional, Bönnemann, Carsten G., additional, and Ottenheijm, Coen A. C., additional

Published
2024
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39. Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease

Author

Chen, Charles D., Joseph-Mathurin, Nelly, Sinha, Namita, Zhou, Aihong, Li, Yan, Friedrichsen, Karl, McCullough, Austin, Franklin, Erin E., Hornbeck, Russ, Gordon, Brian, Sharma, Vijay, Cruchaga, Carlos, Goate, Alison, Karch, Celeste, McDade, Eric, Xiong, Chengjie, Bateman, Randall J., Ghetti, Bernardino, Ringman, John M., Chhatwal, Jasmeer, Masters, Colin L., McLean, Catriona, Lashley, Tammaryn, Su, Yi, Koeppe, Robert, Jack, Clifford, Klunk, William E., Morris, John C., Perrin, Richard J., Cairns, Nigel J., and Benzinger, Tammie L. S.

Published
2021
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41. Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

Author

Kovacs, Gabor G, Xie, Sharon X, Lee, Edward B, Robinson, John L, Caswell, Carrie, Irwin, David J, Toledo, Jon B, Johnson, Victoria E, Smith, Douglas H, Alafuzoff, Irina, Attems, Johannes, Bencze, Janos, Bieniek, Kevin F, Bigio, Eileen H, Bodi, Istvan, Budka, Herbert, Dickson, Dennis W, Dugger, Brittany N, Duyckaerts, Charles, Ferrer, Isidro, Forrest, Shelley L, Gelpi, Ellen, Gentleman, Stephen M, Giaccone, Giorgio, Grinberg, Lea T, Halliday, Glenda M, Hatanpaa, Kimmo J, Hof, Patrick R, Hofer, Monika, Hortobágyi, Tibor, Ironside, James W, King, Andrew, Kofler, Julia, Kövari, Enikö, Kril, Jillian J, Love, Seth, Mackenzie, Ian R, Mao, Qinwen, Matej, Radoslav, McLean, Catriona, Munoz, David G, Murray, Melissa E, Neltner, Janna, Nelson, Peter T, Ritchie, Diane, Rodriguez, Roberta D, Rohan, Zdenek, Rozemuller, Annemieke, Sakai, Kenji, Schultz, Christian, Seilhean, Danielle, Smith, Vanessa, Tacik, Pawel, Takahashi, Hitoshi, Takao, Masaki, Rudolf Thal, Dietmar, Weis, Serge, Wharton, Stephen B, White, Charles L, Woulfe, John M, Yamada, Masahito, and Trojanowski, John Q

Subjects
Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Frontotemporal Dementia (FTD), Aging, Neurodegenerative, Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease, Aged, Aged, 80 and over, Astrocytes, Female, Humans, Male, Middle Aged, Severity of Illness Index, Tauopathies, tau Proteins, ARTAG, Digital pathology, Interrater agreement, Neuropathology, Tau, Tau-astrogliopathy, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

Published
2017

42. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Author

Southey, Melissa C, Goldgar, David E, Winqvist, Robert, Pylkäs, Katri, Couch, Fergus, Tischkowitz, Marc, Foulkes, William D, Dennis, Joe, Michailidou, Kyriaki, van Rensburg, Elizabeth J, Heikkinen, Tuomas, Nevanlinna, Heli, Hopper, John L, Dörk, Thilo, Claes, Kathleen BM, Reis-Filho, Jorge, Teo, Zhi Ling, Radice, Paolo, Catucci, Irene, Peterlongo, Paolo, Tsimiklis, Helen, Odefrey, Fabrice A, Dowty, James G, Schmidt, Marjanka K, Broeks, Annegien, Hogervorst, Frans B, Verhoef, Senno, Carpenter, Jane, Clarke, Christine, Scott, Rodney J, Fasching, Peter A, Haeberle, Lothar, Ekici, Arif B, Beckmann, Matthias W, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Bolla, Manjeet K, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Marme, Federik, Burwinkel, Barbara, Yang, Rongxi, Guénel, Pascal, Truong, Thérèse, Menegaux, Florence, Sanchez, Marie, Bojesen, Stig, Nielsen, Sune F, Flyger, Henrik, Benitez, Javier, Zamora, M Pilar, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Anton-Culver, Hoda, Neuhausen, Susan, Ziogas, Argyrios, Clarke, Christina A, Brenner, Hermann, Arndt, Volker, Stegmaier, Christa, Brauch, Hiltrud, Brüning, Thomas, Ko, Yon-Dschun, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia V, Antonenkova, Natalia N, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Spurdle, Amanda B, Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els, Smeets, Dominiek, Beuselinck, Benoit, Floris, Giuseppe, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Olson, Janet E, Vachon, Celine, Pankratz, Vernon S, McLean, Catriona, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Kristensen, Vessela, Alnæs, Grethe Grenaker, and Zheng, Wei

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Ovarian Cancer, Aging, Breast Cancer, Cancer, Women's Health, Rare Diseases, Prevention, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Ataxia Telangiectasia Mutated Proteins, Breast Neoplasms, Case-Control Studies, Checkpoint Kinase 2, Fanconi Anemia Complementation Group N Protein, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Mutation, Nuclear Proteins, Ovarian Neoplasms, Prostatic Neoplasms, Risk, Tumor Suppressor Proteins, Australian Ovarian Cancer Study Group, Cancer: breast, Cancer: ovary, Cancer: prostate, cancer predisposition, Medical and Health Sciences, Genetics & Heredity, Clinical sciences
Abstract

BackgroundThe rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.MethodsWe genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.ResultsFor European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.ConclusionsThis report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Published
2016

44. Trimethoprim‐sulfamethoxazole acute respiratory distress syndrome requiring lung transplantation.

Author

Donnan, Matthew, Siemienowicz, Miranda, Tay, Hui Sien, McLean, Catriona, Philpot, Steve, Mason, Chris, Snell, Greg, Glaspole, Ian, and Stirling, Rob G.

Subjects
ADULT respiratory distress syndrome, LUNG transplantation, HLA histocompatibility antigens, URINARY tract infections, RESPIRATORY insufficiency, CRITICAL care medicine
Abstract

Trimethoprim‐sulfamethoxazole (TMP‐SMX) acute respiratory distress syndrome (ARDS) is a rare, but severe complication of a commonly prescribed antibiotic. TMP‐SMX typically affects young, otherwise well patients with a specific human leukocyte antigen type (HLA‐B*07:02 and HLA‐C*07:02). The condition is poorly understood with a unique pathological appearance and mechanism that remains unclear. Mortality rate is greater than one third. We describe the case of a previously well 18‐year‐old woman treated with a prolonged course of TMP‐SMX for a complex urinary tract infection who developed rapidly progressive respiratory failure requiring prolonged intensive care admission, extra‐corporeal membranous oxygenation, and eventual lung transplantation. No targeted treatment exists, further research is required to better understand disease pathogenetic mechanisms and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain

Author

De Paoli-Iseppi, Ricardo, primary, Joshi, Shweta S, additional, Gleeson, Josie, additional, Prawer, Yair DJ, additional, You, Yupei, additional, Agarwal, Ria, additional, Li, Anran, additional, Hull, Anthea, additional, Whitehead, Eloise M, additional, Seo, Yoonji, additional, Kujawa, Rhea, additional, Chang, Raphael, additional, Dutt, Mriga, additional, McLean, Catriona, additional, Parker, Benjamin L, additional, and Clark, Michael B, additional

Published
2024
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50. Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia.

Author

Wan, Jijun, Steffen, Janos, Yourshaw, Michael, Mamsa, Hafsa, Andersen, Erik, Rudnik-Schöneborn, Sabine, Pope, Kate, Howell, Katherine B, McLean, Catriona A, Kornberg, Andrew J, Joseph, Jörg, Lockhart, Paul J, Zerres, Klaus, Ryan, Monique M, Nelson, Stanley F, Koehler, Carla M, and Jen, Joanna C

Subjects
Biomedical and Clinical Sciences, Neurosciences, Genetics, Pediatric, Orphan Drug, Neurodegenerative, Rare Diseases, Brain Disorders, Congenital Structural Anomalies, Aetiology, 2.1 Biological and endogenous factors, Neurological, Amino Acids, Animals, Animals, Genetically Modified, Brain, Cell Line, Transformed, Cells, Cultured, Cerebellar Diseases, Cohort Studies, Embryo, Nonmammalian, Female, Genetic Predisposition to Disease, Humans, Infant, Magnetic Resonance Imaging, Male, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, Models, Molecular, Mutation, Phosphate Transport Proteins, Polymorphism, Single Nucleotide, Zebrafish, pontocerebellar hypoplasia, SLC25A46, mitochondria, optic atrophy spectrum disorder, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Disturbed mitochondrial fusion and fission have been linked to various neurodegenerative disorders. In siblings from two unrelated families who died soon after birth with a profound neurodevelopmental disorder characterized by pontocerebellar hypoplasia and apnoea, we discovered a missense mutation and an exonic deletion in the SLC25A46 gene encoding a mitochondrial protein recently implicated in optic atrophy spectrum disorder. We performed functional studies that confirmed the mitochondrial localization and pro-fission properties of SLC25A46. Knockdown of slc24a46 expression in zebrafish embryos caused brain malformation, spinal motor neuron loss, and poor motility. At the cellular level, we observed abnormally elongated mitochondria, which was rescued by co-injection of the wild-type but not the mutant slc25a46 mRNA. Conversely, overexpression of the wild-type protein led to mitochondrial fragmentation and disruption of the mitochondrial network. In contrast to mutations causing non-lethal optic atrophy, missense mutations causing lethal congenital pontocerebellar hypoplasia markedly destabilize the protein. Indeed, the clinical severity appears inversely correlated with the relative stability of the mutant protein. This genotype-phenotype correlation underscores the importance of SLC25A46 and fine tuning of mitochondrial fission and fusion in pontocerebellar hypoplasia and central neurodevelopment in addition to optic and peripheral neuropathy across the life span.

Published
2016

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