Search

Your search keyword '"Ryan, Natalie S"' showing total 482 results
Start Over Author "Ryan, Natalie S"
482 results on '"Ryan, Natalie S"'

1. Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease

Author

Hofmann, Anna, Häsler, Lisa M., Lambert, Marius, Kaeser, Stephan A., Gräber-Sultan, Susanne, Obermüller, Ulrike, Kuder-Buletta, Elke, la Fougere, Christian, Laske, Christoph, Vöglein, Jonathan, Levin, Johannes, Fox, Nick C., Ryan, Natalie S., Zetterberg, Henrik, Llibre-Guerra, Jorge J., Perrin, Richard J., Ibanez, Laura, Schofield, Peter R., Brooks, William S., Day, Gregory S., Farlow, Martin R., Allegri, Ricardo F., Chrem Mendez, Patricio, Ikeuchi, Takeshi, Kasuga, Kensaku, Lee, Jae-Hong, Roh, Jee Hoon, Mori, Hiroshi, Lopera, Francisco, Bateman, Randall J., McDade, Eric, Gordon, Brian A., Chhatwal, Jasmeer P., Jucker, Mathias, and Schultz, Stephanie A.

Published
2024
Full Text
View/download PDF

3. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo

Subjects
Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022

4. γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS)

Author

Aguillon, David, Allegri, Ricardo F., Aschenbrenner, Andrew J., Baker, Bryce, Barthelemy, Nicolas, Bechara, Jacob A., Berman, Sarah B., Brooks, William S., Cash, David M., Chen, Allison, Chrem Mendez, Patricio, Courtney, Laura, Cruchaga, Carlos, Daniels, Alisha J., Fagan, Anne M., Flores, Shaney, Fox, Nick C., Franklin, Erin, Goate, Alison M., Graber-Sultan, Susanne, Graff-Radford, Neill R., Gremminger, Emily, Herries, Elizabeth, Hofmann, Anna, Holtzman, David M., Hornbeck, Russ, Huey, Edward D., Ibanez, Laura, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jackson, Kelley, Jarman, Steve, Jerome, Gina, Johnson, Erik C.B, Kasuga, Kensaku, Keefe, Sarah, Koudelis, Deborah, Kuder-Buletta, Elke, Laske, Christoph, Leon, Yudy Milena, Levey, Allan I., Li, Yan, Llibre-Guerra, Jorge J., Lopera, Francisco, Lu, Ruijin, Marsh, Jacob, Martins, Ralph, Massoumzadeh, Parinaz, Masters, Colin, McCullough, Austin, McKay, Nicole, Minton, Matthew, Mori, Hiroshi, Morris, John C., Nadkarni, Neelesh K., Nicklaus, Joyce, Niimi, Yoshiki, Noble, James M., Obermueller, Ulrike, Picarello, Danielle M., Pulizos, Christine, Ramirez, Laura, Renton, Alan E., Ringman, John, Rizzo, Jacqueline, Roedenbeck, Yvonne, Roh, Jee Hoon, Rosa-Neto, Pedro, Ryan, Natalie S., Sabaredzovic, Edita, Salloway, Stephen, Sanchez-Valle, Raquel, Scott, Jalen, Seyfried, Nicholas T., Simmons, Ashlee, Smith, Jennifer, Smith, Hunter, Stauber, Jennifer, Stout, Sarah, Supnet-Bell, Charlene, Surace, Ezequiel, Vazquez, Silvia, Vöglein, Jonathan, Wang, Guoqiao, Wang, Qing, Xu, Xiong, Xu, Jinbin, Schultz, Stephanie A, Liu, Lei, Schultz, Aaron P, Fitzpatrick, Colleen D, Levin, Raina, Bellier, Jean-Pierre, Shirzadi, Zahra, Joseph-Mathurin, Nelly, Chen, Charles D, Benzinger, Tammie L S, Day, Gregory S, Farlow, Martin R, Gordon, Brian A, Hassenstab, Jason J, Jack, Clifford R, Jr, Jucker, Mathias, Karch, Celeste M, Lee, Jae-Hong, Levin, Johannes, Perrin, Richard J, Schofield, Peter R, Xiong, Chengjie, Johnson, Keith A, McDade, Eric, Bateman, Randall J, Sperling, Reisa A, Selkoe, Dennis J, and Chhatwal, Jasmeer P

Published
2024
Full Text
View/download PDF

5. Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study

Author

Aizenstein, Howard J., Andrews, Howard F., Bell, Karen, Birn, Rasmus M., Bulova, Peter, Cheema, Amrita, Chen, Kewei, Clare, Isabel, Clark, Lorraine, Cohen, Ann D., Constantino, John N., Doran, Eric W., Feingold, Eleanor, Foroud, Tatiana M., Hartley, Sigan L., Hom, Christy, Honig, Lawrence, Ikonomovic, Milos D., Johnson, Sterling C., Jordan, Courtney, Kamboh, M. Ilyas, Keator, David, Klunk, William E., Kofler, Julia K., Kreisl, William C., Krinsky-McHale, Sharon J., Lao, Patrick, Laymon, Charles, Lott, Ira T., Lupson, Victoria, Mathis, Chester A., Minhas, Davneet S., Nadkarni, Neelesh, Pang, Deborah, Petersen, Melissa, Price, Julie C., Pulsifer, Margaret, Reiman, Eric, Rizvi, Batool, Sabbagh, Marwan N., Schupf, Nicole, Tudorascu, Dana L., Tumuluru, Rameshwari, Tycko, Benjamin, Varadarajan, Badri, White, Desiree A., Yassa, Michael A., Zaman, Shahid, Zhang, Fan, Bateman, Randall, Daniels, Alisha J., Courtney, Laura, McDade, Eric, Llibre-Guerra, Jorge J., Supnet-Bell, Charlene, Xiong, Chengie, Xu, Xiong, Lu, Ruijin, Wang, Guoqiao, Li, Yan, Gremminger, Emily, Perrin, Richard J., Franklin, Erin, Ibanez, Laura, Jerome, Gina, Herries, Elizabeth, Stauber, Jennifer, Baker, Bryce, Minton, Matthew, Cruchaga, Carlos, Goate, Alison M., Renton, Alan E., Picarello, Danielle M., Benzinger, Tammie, Gordon, Brian A., Hornbeck, Russall, Hassenstab, Jason, Smith, Jennifer, Stout, Sarah, Aschenbrenner, Andrew J., Karch, Celeste M., Marsh, Jacob, Morris, John C., Holtzman, David M., Barthelemy, Nicolas, Xu, Jinbin, Noble, James M., Berman, Sarah B., Ikonomovic, Snezana, Nadkarni, Neelesh K., Day, Gregory, Graff-Radford, Neill R., Farlow, Martin, Chhatwal, Jasmeer P., Ikeuchi, Takeshi, Kasuga, Kensaku, Niimi, Yoshiki, Huey, Edward D., Salloway, Stephen, Schofield, Peter R., Brooks, William S., Bechara, Jacob A., Martins, Ralph, Fox, Nick C., Cash, David M., Ryan, Natalie S., Jucker, Mathias, Laske, Christoph, Hofmann, Anna, Kuder-Buletta, Elke, Graber-Sultan, Susanne, Obermueller, Ulrike, Levin, Johannes, Roedenbeck, Yvonne, Vöglein, Jonathan, Lee, Jae-Hong, Roh, Jee Hoon, Sanchez-Valle, Raquel, Rosa-Neto, Pedro, Allegri, Ricardo F., Chrem Mendez, Patricio, Surace, Ezequiel, Vazquez, Silvia, Lopera, Francisco, Leon, Yudy Milena, Ramirez, Laura, Aguillon, David, Levey, Allan I., Johnson, Erik C.B, Seyfried, Nicholas T., Ringman, John, Mori, Hiroshi, Wisch, Julie K, McKay, Nicole S, Boerwinkle, Anna H, Kennedy, James, Flores, Shaney, Handen, Benjamin L, Christian, Bradley T, Head, Elizabeth, Mapstone, Mark, Rafii, Michael S, O’Bryant, Sid E, Price, Julie C, Laymon, Charles M, Krinsky-McHale, Sharon J, Lai, Florence, Rosas, H Diana, Hartley, Sigan L, Lott, Ira T, Tudorascu, Dana, Zammit, Matthew, Brickman, Adam M, Lee, Joseph H, Bird, Thomas D, Cohen, Annie, Chrem, Patricio, Daniels, Alisha, Chhatwal, Jasmeer P, Karch, Celeste M, Day, Gregory S, Llibre-Guerra, Jorge, Ringman, John M, van Dyck, Christopher H, Xiong, Chengjie, Morris, John C, Bateman, Randall J, Benzinger, Tammie L S, Gordon, Brian A, and Ances, Beau M

Published
2024
Full Text
View/download PDF

6. Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy.

Author

Firth, Nicholas C, Primativo, Silvia, Marinescu, Razvan-Valentin, Shakespeare, Timothy J, Suarez-Gonzalez, Aida, Lehmann, Manja, Carton, Amelia, Ocal, Dilek, Pavisic, Ivanna, Paterson, Ross W, Slattery, Catherine F, Foulkes, Alexander JM, Ridha, Basil H, Gil-Néciga, Eulogio, Oxtoby, Neil P, Young, Alexandra L, Modat, Marc, Cardoso, M Jorge, Ourselin, Sebastien, Ryan, Natalie S, Miller, Bruce L, Rabinovici, Gil D, Warrington, Elizabeth K, Rossor, Martin N, Fox, Nick C, Warren, Jason D, Alexander, Daniel C, Schott, Jonathan M, Yong, Keir XX, and Crutch, Sebastian J

Subjects
Cerebral Cortex, Humans, Alzheimer Disease, Disease Progression, Magnetic Resonance Imaging, Case-Control Studies, Longitudinal Studies, Neuropsychological Tests, Models, Neurological, Middle Aged, Female, Male, Cognitive Dysfunction, Alzheimer’s disease, brain atrophy, dementia, memory, structural MRI, Alzheimer's disease, Models, Neurological, Neurology & Neurosurgery, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.

Published
2019

9. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study

Author

O’Connor, Antoinette, Karikari, Thomas K., Poole, Teresa, Ashton, Nicholas J., Lantero Rodriguez, Juan, Khatun, Ayesha, Swift, Imogen, Heslegrave, Amanda J., Abel, Emily, Chung, Elisha, Weston, Philip S. J., Pavisic, Ivanna M., Ryan, Natalie S., Barker, Suzie, Rossor, Martin N., Polke, James M., Frost, Chris, Mead, Simon, Blennow, Kaj, Zetterberg, Henrik, and Fox, Nick C.

Published
2021
Full Text
View/download PDF

10. Consensus classification of posterior cortical atrophy

Author

Crutch, Sebastian J, Schott, Jonathan M, Rabinovici, Gil D, Murray, Melissa, Snowden, Julie S, van der Flier, Wiesje M, Dickerson, Bradford C, Vandenberghe, Rik, Ahmed, Samrah, Bak, Thomas H, Boeve, Bradley F, Butler, Christopher, Cappa, Stefano F, Ceccaldi, Mathieu, de Souza, Leonardo Cruz, Dubois, Bruno, Felician, Olivier, Galasko, Douglas, Graff‐Radford, Jonathan, Graff‐Radford, Neill R, Hof, Patrick R, Krolak‐Salmon, Pierre, Lehmann, Manja, Magnin, Eloi, Mendez, Mario F, Nestor, Peter J, Onyike, Chiadi U, Pelak, Victoria S, Pijnenburg, Yolande, Primativo, Silvia, Rossor, Martin N, Ryan, Natalie S, Scheltens, Philip, Shakespeare, Timothy J, González, Aida Suárez, Tang‐Wai, David F, Yong, Keir XX, Carrillo, Maria, Fox, Nick C, and Area, Alzheimer's Association ISTAART Atypical Alzheimer's Disease and Associated Syndromes Professional Interest

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Rare Diseases, Neurosciences, Neurodegenerative, Neurological, Brain, Brain Diseases, Humans, Posterior cortical atrophy, Alzheimer's disease, Clinico-radiological syndrome, Pathophysiology, Biomarker, Alzheimer's Association ISTAART Atypical Alzheimer's Disease and Associated Syndromes Professional Interest Area, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionA classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.MethodsConsensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA.ResultsA three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum.DiscussionThere was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.

Published
2017

13. The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations.

Author

Arber, Charles, Belder, Christopher R. S., Tomczuk, Filip, Gabriele, Rebecca, Buhidma, Yazead, Farrell, Clíona, O'Connor, Antoinette, Rice, Helen, Lashley, Tammaryn, Fox, Nick C., Ryan, Natalie S., and Wray, Selina

Abstract

INTRODUCTION: Familial Alzheimer's disease (fAD) is heterogeneous in terms of age at onset and clinical presentation. A greater understanding of the pathogenicity of fAD variants and how these contribute to heterogeneity will enhance our understanding of the mechanisms of AD more widely. METHODS: To determine the pathogenicity of the unclassified PSEN1 P436S mutation, we studied an expanded kindred of eight affected individuals, with magnetic resonance imaging (MRI) (two individuals), patient‐derived induced pluripotent stem cell (iPSC) models (two donors), and post‐mortem histology (one donor). RESULTS: An autosomal dominant pattern of inheritance of fAD was seen, with an average age at symptom onset of 46 years and atypical features. iPSC models and post‐mortem tissue supported high production of amyloid beta 43 (Aβ43). PSEN1 peptide maturation was unimpaired. DISCUSSION: We confirm that the P436S mutation in PSEN1 causes atypical fAD. The location of the mutation in the critical PSEN1 proline‐alanine‐leucine‐proline (PALP) motif may explain the early age at onset despite appropriate protein maturation. Highlights: PSEN1 P436S mutations cause familial Alzheimer's disease.This mutation is associated with atypical clinical presentation.Induced pluripotent stem cells (iPSCs) and post‐mortem studies support increased amyloid beta (Aβ43) production.Early age at onset highlights the importance of the PALP motif in PSEN1 function. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

17. The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations

Author

Arber, Charles, primary, Belder, Christopher R.S., additional, Tomczuk, Filip, additional, Gabriele, Rebecca, additional, Buhidma, Yazead, additional, O'Connor, Antoinette, additional, Rice, Helen, additional, Lashley, Tammaryn, additional, Fox, Nick C., additional, Ryan, Natalie S., additional, and Wray, Selina, additional

Published
2023
Full Text
View/download PDF

18. Atypical presentations of autosomal dominant familial Alzheimer’s disease: insights into genetic, neuropathological and clinical heterogeneity

Author

Ryan, Natalie S, primary, Willumsen, Nanet, additional, Nicholas, Jennifer M, additional, Poole, Teresa, additional, Pavisic, Ivanna M, additional, Walsh, Phoebe, additional, Rice, Helen, additional, Lu, Kirsty, additional, O'Connor, Antoinette, additional, Weston, Philip SJ, additional, Abel, Emily, additional, Barkhof, Frederik, additional, Barnes, Jo, additional, Lashley, Tammaryn, additional, and Fox, Nick C, additional

Published
2023
Full Text
View/download PDF

19. Creation of an open-access, mutation-defined fibroblast resource for neurological disease research.

Author

Wray, Selina, Self, Matthew, NINDS Parkinson's Disease iPSC Consortium, NINDS Huntington's Disease iPSC Consortium, NINDS ALS iPSC Consortium, Lewis, Patrick A, Taanman, Jan-Willem, Ryan, Natalie S, Mahoney, Colin J, Liang, Yuying, Devine, Michael J, Sheerin, Una-Marie, Houlden, Henry, Morris, Huw R, Healy, Daniel, Marti-Masso, Jose-Felix, Preza, Elisavet, Barker, Suzanne, Sutherland, Margaret, Corriveau, Roderick A, D'Andrea, Michael, Schapira, Anthony HV, Uitti, Ryan J, Guttman, Mark, Opala, Grzegorz, Jasinska-Myga, Barbara, Puschmann, Andreas, Nilsson, Christer, Espay, Alberto J, Slawek, Jaroslaw, Gutmann, Ludwig, Boeve, Bradley F, Boylan, Kevin, Stoessl, A Jon, Ross, Owen A, Maragakis, Nicholas J, Van Gerpen, Jay, Gerstenhaber, Melissa, Gwinn, Katrina, Dawson, Ted M, Isacson, Ole, Marder, Karen S, Clark, Lorraine N, Przedborski, Serge E, Finkbeiner, Steven, Rothstein, Jeffrey D, Wszolek, Zbigniew K, Rossor, Martin N, and Hardy, John

Subjects
NINDS Parkinson's Disease iPSC Consortium, NINDS Huntington's Disease iPSC Consortium, NINDS ALS iPSC Consortium, Cell Line, Fibroblasts, Humans, Nervous System Diseases, Biopsy, Immunohistochemistry, Cell Differentiation, Cell Proliferation, Mutation, Models, Genetic, Access to Information, Databases, Factual, Tissue Banks, Induced Pluripotent Stem Cells, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Genetics, Stem Cell Research, Neurosciences, Brain Disorders, Aetiology, 2.6 Resources and infrastructure (aetiology), 2.1 Biological and endogenous factors, Generic health relevance, Neurological, General Science & Technology
Abstract

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.

Published
2012

26. First presentation with neuropsychiatric symptoms in autosomal dominant Alzheimer's disease: The Dominantly Inherited Alzheimer's Network Study

Author

O'Connor, Antoinette, Rice, Helen, Barnes, Josephine, Ryan, Natalie S., Liu, Kathy Y., Allegri, Ricardo Francisco, Berman, Sarah, Ringman, John M., Cruchaga, Carlos, Farlow, Martin R., Hassenstab, Jason, Lee, Jae-Hong, Perrin, Richard J., Xiong, Chengjie, Gordon, Brian, Levey, Allan I., Goate, Alison, Graff-Radford, Neil, Levin, Johannes, Jucker, Mathias, Benzinger, Tammie, McDade, Eric, Mori, Hiroshi, Noble, James M., Schofield, Peter R., Martins, Ralph N., Salloway, Stephen, Chhatwal, Jasmeer, Morris, John C., Bateman, Randall, Howard, Rob, Reeves, Suzanne, Fox, Nick C., O'Connor, Antoinette, Rice, Helen, Barnes, Josephine, Ryan, Natalie S., Liu, Kathy Y., Allegri, Ricardo Francisco, Berman, Sarah, Ringman, John M., Cruchaga, Carlos, Farlow, Martin R., Hassenstab, Jason, Lee, Jae-Hong, Perrin, Richard J., Xiong, Chengjie, Gordon, Brian, Levey, Allan I., Goate, Alison, Graff-Radford, Neil, Levin, Johannes, Jucker, Mathias, Benzinger, Tammie, McDade, Eric, Mori, Hiroshi, Noble, James M., Schofield, Peter R., Martins, Ralph N., Salloway, Stephen, Chhatwal, Jasmeer, Morris, John C., Bateman, Randall, Howard, Rob, Reeves, Suzanne, and Fox, Nick C.

Abstract

Behavioural changes and neuropsychiatric symptoms (NPS) commonly occur in Alzheimer’s disease (AD) but may not be recognised as AD-related when they are the presenting feature. NPS are important as they are associated with greater functional impairment, poorer quality of life, accelerated cognitive decline and worsened caregiver burden.1 Autosomal dominant AD (ADAD), although < 1% of total AD cases, provides a valuable opportunity to study the clinical heterogeneity of AD. The young age at onset reduces the prevalence of age-related comorbid pathologies and the near 100% penetrance of pathogenic mutations reduces the likelihood of misdiagnosis.2 Anxiety and depression commonly occur in ADAD family members, with increased levels of depression having been found among predementia female mutation carriers.3 Subsequent studies, however, have shown that anxiety and/or depression are common regardless of mutation status, occurring in almost one in three at-risk individuals, with one study reporting a higher rate of depression in non-carriers (17%) than asymptomatic carriers (5%).4 5 Despite the high frequency of NPS in ADAD families, relatively little is known about the proportion of ADAD cases who present with predominantly behavioural symptoms. Our aims were to assess the first reported clinical change in symptomatic ADAD, to compare presentations across genotypes, and to compare cognitive performance between behavioural and cognitive-led presentations.

Published
2023

28. Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease

Author

Schott, Jonathan M., Crutch, Sebastian J., Carrasquillo, Minerva M., Uphill, James, Shakespeare, Tim J., Ryan, Natalie S., Yong, Keir X., Lehmann, Manja, Ertekin-Taner, Nilufer, Graff-Radford, Neill R., Boeve, Bradley F., Murray, Melissa E., Khan, Qurat ul Ain, Petersen, Ronald C., Dickson, Dennis W., Knopman, David S., Rabinovici, Gil D., Miller, Bruce L., González, Aida Suárez, Gil-Néciga, Eulogio, Snowden, Julie S., Harris, Jenny, Pickering-Brown, Stuart M., Louwersheimer, Eva, van der Flier, Wiesje M., Scheltens, Philip, Pijnenburg, Yolande A., Galasko, Douglas, Sarazin, Marie, Dubois, Bruno, Magnin, Eloi, Galimberti, Daniela, Scarpini, Elio, Cappa, Stefano F., Hodges, John R., Halliday, Glenda M., Bartley, Lauren, Carrillo, Maria C., Bras, Jose T., Hardy, John, Rossor, Martin N., Collinge, John, Fox, Nick C., and Mead, Simon

Published
2016
Full Text
View/download PDF

31. Clinical considerations in early-onset cerebral amyloid angiopathy.

Author

Banerjee, Gargi, Collinge, John, Fox, Nick C, Lashley, Tammaryn, Mead, Simon, Schott, Jonathan M, Werring, David J, and Ryan, Natalie S

Subjects
CEREBRAL amyloid angiopathy, CEREBRAL small vessel diseases, MEDICAL personnel, DNA copy number variations, ALZHEIMER'S disease, MISSENSE mutation
Abstract

Cerebral amyloid angiopathy (CAA) is an important cerebral small vessel disease associated with brain haemorrhage and cognitive change. The commonest form, sporadic amyloid-β CAA, usually affects people in mid- to later life. However, early-onset forms, though uncommon, are increasingly recognized and may result from genetic or iatrogenic causes that warrant specific and focused investigation and management. In this review, we firstly describe the causes of early-onset CAA, including monogenic causes of amyloid-β CAA (APP missense mutations and copy number variants; mutations of PSEN1 and PSEN2) and non-amyloid-β CAA (associated with ITM2B , CST3 , GSN , PRNP and TTR mutations), and other unusual sporadic and acquired causes including the newly-recognized iatrogenic subtype. We then provide a structured approach for investigating early-onset CAA, and highlight important management considerations. Improving awareness of these unusual forms of CAA amongst healthcare professionals is essential for facilitating their prompt diagnosis, and an understanding of their underlying pathophysiology may have implications for more common, late-onset, forms of the disease. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

34. First presentation with neuropsychiatric symptoms in autosomal dominant Alzheimer’s disease: the Dominantly Inherited Alzheimer’s Network Study

Author

O'Connor, Antoinette, primary, Rice, Helen, additional, Barnes, Josephine, additional, Ryan, Natalie S, additional, Liu, Kathy Y, additional, Allegri, Ricardo Francisco, additional, Berman, Sarah, additional, Ringman, John M, additional, Cruchaga, Carlos, additional, Farlow, Martin R, additional, Hassenstab, Jason, additional, Lee, Jae-Hong, additional, Perrin, Richard J, additional, Xiong, Chengjie, additional, Gordon, Brian, additional, Levey, Allan I, additional, Goate, Alison, additional, Graff-Radford, Neil, additional, Levin, Johannes, additional, Jucker, Mathias, additional, Benzinger, Tammie, additional, McDade, Eric, additional, Mori, Hiroshi, additional, Noble, James M, additional, Schofield, Peter R, additional, Martins, Ralph N, additional, Salloway, Stephen, additional, Chhatwal, Jasmeer, additional, Morris, John C, additional, Bateman, Randall, additional, Howard, Rob, additional, Reeves, Suzanne, additional, and Fox, Nick C, additional

Published
2022
Full Text
View/download PDF

35. The PSEN1 E280G mutation leads to increased amyloid-β43 production in induced pluripotent stem cell neurons and deposition in brain tissue

Author

Willumsen, Nanet, primary, Arber, Charles, additional, Lovejoy, Christopher, additional, Toombs, Jamie, additional, Alatza, Argyro, additional, Weston, Philip S J, additional, Chávez-Gutiérrez, Lucia, additional, Hardy, John, additional, Zetterberg, Henrik, additional, Fox, Nick C, additional, Ryan, Natalie S, additional, Lashley, Tammaryn, additional, and Wray, Selina, additional

Published
2022
Full Text
View/download PDF

37. Clinical and genetic features of Lewy body pathology in autosomal dominant and sporadic Alzheimer disease

Author

Vöglein, Jonathan, primary, Ryan, Natalie S, additional, Bateman, Randall J., additional, Paumier, Katrina L., additional, Cairns, Nigel J, additional, Franklin, Erin E., additional, Perrin, Richard J., additional, Xiong, Chengjie, additional, Jucker, Mathias, additional, Lashley, Tammaryn, additional, Arzberger, Thomas, additional, Herms, Jochen, additional, Dieterich, Marianne, additional, Höglinger, Günter, additional, Danek, Adrian, additional, Morris, John C., additional, Fox, Nick C, additional, and Levin, Johannes, additional

Published
2022
Full Text
View/download PDF

38. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W., Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C., Damotte, Vincent, Naj, Adam C., Boland, Anne, Vronskaya, Maria, van der Lee, Sven J., Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R., Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L., Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B., Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N., Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W., Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L., Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V., Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C., Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T., Adams, Hieab H., Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A., Dombroski, Beth A., Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B., Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S., Meslage, Stéphane, Kornhuber, Johannes, White, Charles C., Song, Yuenjoo, Barber, Robert C., Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M., Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L. Adrienne, Albert, Marilyn S., De Deyn, Peter P., Gu, Wei, Himali, Jayanadra J., Beekly, Duane, Squassina, Alessio, Hartmann, Annette M., Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E., Doody, Rachelle S., Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J., Benito, Yolanda A., Holmes, Clive, Karamujić-Čomić, Hata, Frosch, Matthew P., Thonberg, Hakan, Maier, Wolfgang, Roshchupkin, Gennady, Ghetti, Bernardino, Giedraitis, Vilmantas, Kawalia, Amit, Li, Shuo, Huebinger, Ryan M., Kilander, Lena, Moebus, Susanne, Hernández, Isabel, Kamboh, M. Ilyas, Brundin, RoseMarie, Turton, James, Yang, Qiong, Katz, Mindy J., Concari, Letizia, Lord, Jenny, Beiser, Alexa S., Keene, C. Dirk, Helisalmi, Seppo, Kloszewska, Iwona, Kukull, Walter A., Koivisto, Anne Maria, Lynch, Aoibhinn, Tarraga, Lluís, Larson, Eric B., Haapasalo, Annakaisa, Lawlor, Brian, Mosley, Thomas H., Lipton, Richard B., Solfrizzi, Vincenzo, Gill, Michael, Longstreth, Jr, W. T., Montine, Thomas J., Frisardi, Vincenza, Diez-Fairen, Monica, Rivadeneira, Fernando, Petersen, Ronald C., Deramecourt, Vincent, Alvarez, Ignacio, Salani, Francesca, Ciaramella, Antonio, Boerwinkle, Eric, Reiman, Eric M., Fievet, Nathalie, Rotter, Jerome I., Reisch, Joan S., Hanon, Olivier, Cupidi, Chiara, Uitterlinden, A. G. Andre, Royall, Donald R., Dufouil, Carole, Maletta, Raffaele Giovanni, de Rojas, Itziar, Sano, Mary, Brice, Alexis, Cecchetti, Roberta, George-Hyslop, Peter St, Ritchie, Karen, Tsolaki, Magda, Tsuang, Debby W., Dubois, Bruno, Craig, David, Wu, Chuang-Kuo, Soininen, Hilkka, Avramidou, Despoina, Albin, Roger L., Fratiglioni, Laura, Germanou, Antonia, Apostolova, Liana G., Keller, Lina, Koutroumani, Maria, Arnold, Steven E., Panza, Francesco, Gkatzima, Olymbia, Asthana, Sanjay, Hannequin, Didier, Whitehead, Patrice, Atwood, Craig S., Caffarra, Paolo, Hampel, Harald, Quintela, Inés, Carracedo, Ángel, Lannfelt, Lars, Rubinsztein, David C., Barnes, Lisa L., Pasquier, Florence, Frölich, Lutz, Barral, Sandra, McGuinness, Bernadette, Beach, Thomas G., Johnston, Janet A., Becker, James T., Passmore, Peter, Bigio, Eileen H., Schott, Jonathan M., Bird, Thomas D., Warren, Jason D., Boeve, Bradley F., Lupton, Michelle K., Bowen, James D., Proitsi, Petra, Boxer, Adam, Powell, John F., Burke, James R., Kauwe, John S. K., Burns, Jeffrey M., Mancuso, Michelangelo, Buxbaum, Joseph D., Bonuccelli, Ubaldo, Cairns, Nigel J., McQuillin, Andrew, Cao, Chuanhai, Livingston, Gill, Carlson, Chris S., Bass, Nicholas J., Carlsson, Cynthia M., Hardy, John, Carney, Regina M., Bras, Jose, Carrasquillo, Minerva M., Guerreiro, Rita, Allen, Mariet, Chui, Helena C., Fisher, Elizabeth, Masullo, Carlo, Crocco, Elizabeth A., DeCarli, Charles, Bisceglio, Gina, Dick, Malcolm, Ma, Li, Duara, Ranjan, Graff-Radford, Neill R., Evans, Denis A., Hodges, Angela, Faber, Kelley M., Scherer, Martin, Fallon, Kenneth B., Riemenschneider, Matthias, Fardo, David W., Heun, Reinhard, Farlow, Martin R., Kölsch, Heike, Ferris, Steven, Leber, Markus, Foroud, Tatiana M., Heuser, Isabella, Galasko, Douglas R., Giegling, Ina, Gearing, Marla, Hüll, Michael, Geschwind, Daniel H., Gilbert, John R., Morris, John, Green, Robert C., Mayo, Kevin, Growdon, John H., Feulner, Thomas, Hamilton, Ronald L., Harrell, Lindy E., Drichel, Dmitriy, Honig, Lawrence S., Cushion, Thomas D., Huentelman, Matthew J., Hollingworth, Paul, Hulette, Christine M., Hyman, Bradley T., Marshall, Rachel, Jarvik, Gail P., Meggy, Alun, Abner, Erin, Menzies, Georgina E., Jin, Lee-Way, Leonenko, Ganna, Real, Luis M., Jun, Gyungah R., Baldwin, Clinton T., Grozeva, Detelina, Karydas, Anna, Russo, Giancarlo, Kaye, Jeffrey A., Kim, Ronald, Jessen, Frank, Kowall, Neil W., Vellas, Bruno, Kramer, Joel H., Vardy, Emma, LaFerla, Frank M., Jöckel, Karl-Heinz, Lah, James J., Dichgans, Martin, Leverenz, James B., Mann, David, Levey, Allan I., Pickering-Brown, Stuart, Lieberman, Andrew P., Klopp, Norman, Lunetta, Kathryn L., Wichmann, H-Erich, Lyketsos, Constantine G., Morgan, Kevin, Marson, Daniel C., Brown, Kristelle, Martiniuk, Frank, Medway, Christopher, Mash, Deborah C., Nöthen, Markus M., Masliah, Eliezer, Hooper, Nigel M., McCormick, Wayne C., Daniele, Antonio, McCurry, Susan M., Bayer, Anthony, McDavid, Andrew N., Gallacher, John, McKee, Ann C., van den Bussche, Hendrik, Mesulam, Marsel, Brayne, Carol, Miller, Bruce L., Riedel-Heller, Steffi, Miller, Carol A., Miller, Joshua W., Al-Chalabi, Ammar, Morris, John C., Shaw, Christopher E., Myers, Amanda J., Wiltfang, Jens, O’Bryant, Sid, Olichney, John M., Alvarez, Victoria, Parisi, Joseph E., Singleton, Andrew B., Paulson, Henry L., Collinge, John, Perry, William R., Mead, Simon, Peskind, Elaine, Cribbs, David H., Rossor, Martin, Pierce, Aimee, Ryan, Natalie S., Poon, Wayne W., Nacmias, Benedetta, Potter, Huntington, Sorbi, Sandro, Quinn, Joseph F., Sacchinelli, Eleonora, Raj, Ashok, Spalletta, Gianfranco, Raskind, Murray, Caltagirone, Carlo, Bossù, Paola, Orfei, Maria Donata, Reisberg, Barry, Clarke, Robert, Reitz, Christiane, Smith, A David, Ringman, John M., Warden, Donald, Roberson, Erik D., Wilcock, Gordon, Rogaeva, Ekaterina, Bruni, Amalia Cecilia, Rosen, Howard J., Gallo, Maura, Rosenberg, Roger N., Ben-Shlomo, Yoav, Sager, Mark A., Mecocci, Patrizia, Saykin, Andrew J., Pastor, Pau, Cuccaro, Michael L., Vance, Jeffery M., Schneider, Julie A., Schneider, Lori S., Slifer, Susan, Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tang, Mitchell, Tanzi, Rudolph E., Trojanowski, John Q., Troncoso, Juan C., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Wilhelmsen, Kirk C., Williamson, Jennifer, Wingo, Thomas S., Woltjer, Randall L., Wright, Clinton B., Yu, Chang-En, Yu, Lei, Saba, Yasaman, Alzheimer Disease Genetics Consortium (ADGC), The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Pilotto, Alberto, Bullido, Maria J., Peters, Oliver, Crane, Paul K., Bennett, David, Bosco, Paola, Coto, Eliecer, Boccardi, Virginia, De Jager, Phil L., Lleo, Alberto, Warner, Nick, Lopez, Oscar L., Ingelsson, Martin, Deloukas, Panagiotis, Cruchaga, Carlos, Graff, Caroline, Gwilliam, Rhian, Fornage, Myriam, Goate, Alison M., Sanchez-Juan, Pascual, Kehoe, Patrick G., Amin, Najaf, Ertekin-Taner, Nilifur, Berr, Claudine, Debette, Stéphanie, Love, Seth, Launer, Lenore J., Younkin, Steven G., Dartigues, Jean-Francois, Corcoran, Chris, Ikram, M. Arfan, Dickson, Dennis W., Nicolas, Gael, Campion, Dominique, Tschanz, JoAnn, Schmidt, Helena, Hakonarson, Hakon, Clarimon, Jordi, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay A., Van Broeckhoven, Christine, O’Donovan, Michael C., DeStefano, Anita L., Jones, Lesley, Haines, Jonathan L., Deleuze, Jean-Francois, Owen, Michael J., Gudnason, Vilmundur, Mayeux, Richard, Escott-Price, Valentina, Psaty, Bruce M., Ramirez, Alfredo, Wang, Li-San, Ruiz, Agustin, van Duijn, Cornelia M., Holmans, Peter A., Seshadri, Sudha, Williams, Julie, Amouyel, Phillippe, Schellenberg, Gerard D., Lambert, Jean-Charles, and Pericak-Vance, Margaret A.

Published
2019
Full Text
View/download PDF

39. Chemical traits of cerebral amyloid angiopathy in familial British‐, Danish‐, and non‐Alzheimerʼs dementias

Author

Michno, Wojciech, primary, Koutarapu, Srinivas, additional, Camacho, Rafael, additional, Toomey, Christina, additional, Stringer, Katie, additional, Minta, Karolina, additional, Ge, Junyue, additional, Jha, Durga, additional, Fernandez‐Rodriguez, Julia, additional, Brinkmalm, Gunnar, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Ryan, Natalie S., additional, Lashley, Tammaryn, additional, and Hanrieder, Jörg, additional

Published
2022
Full Text
View/download PDF

40. Shining a light on posterior cortical atrophy

Author

Crutch, Sebastian J., Schott, Jonathan M., Rabinovici, Gil D., Boeve, Bradley F., Cappa, Stefano F., Dickerson, Bradford C., Dubois, Bruno, Graff-Radford, Neill R., Krolak-Salmon, Pierre, Lehmann, Manja, Mendez, Mario F., Pijnenburg, Yolande, Ryan, Natalie S., Scheltens, Philip, Shakespeare, Tim, Tang-Wai, David F., van der Flier, Wiesje M., Bain, Lisa, Carrillo, Maria C., and Fox, Nick C.

Published
2013
Full Text
View/download PDF

46. White Matter Hyperintensities Are a Core Feature of Alzheimerʼs Disease: Evidence from the Dominantly Inherited Alzheimer Network

Author

Lee, Seonjoo, Viqar, Fawad, Zimmerman, Molly E., Narkhede, Atul, Tosto, Giuseppe, Benzinger, Tammie L.S., Marcus, Daniel S., Fagan, Anne M., Goate, Alison, Fox, Nick C., Cairns, Nigel J., Holtzman, David M., Buckles, Virginia, Ghetti, Bernardino, McDade, Eric, Martins, Ralph N., Saykin, Andrew J., Masters, Colin L., Ringman, John M., Ryan, Natalie S., Förster, Stefan, Laske, Christoph, Schofield, Peter R., Sperling, Reisa A., Salloway, Stephen, Correia, Stephen, Jack, Clifford, Jr., Weiner, Michael, Bateman, Randall J., Morris, John C., Mayeux, Richard, and Brickman, Adam M.

Published
2016
Full Text
View/download PDF

48. Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease

Author

Willumsen, Nanet, Poole, Teresa, Nicholas, Jennifer M, Fox, Nick C, Ryan, Natalie S, and Lashley, Tammaryn

Subjects
mental disorders
Abstract

Familial Alzheimer's disease (FAD) is caused by autosomal dominant mutations in the PSEN1, PSEN2 or APP genes, giving rise to considerable clinical and pathological heterogeneity in FAD. Here we investigate variability in clinical data and the type and distribution of Aβ pathologies throughout the cortical layers of different FAD mutation cases. Brain tissue from 20 FAD cases [PSEN1 pre-codon 200 (n = 10), PSEN1 post-codon 200 (n = 6), APP (n = 4)] were investigated. Frontal cortex sections were stained immunohistochemically for Aβ, and Nissl to define the cortical layers. The frequency of different amyloid-beta plaque types was graded for each cortical layer and the severity of cerebral amyloid angiopathy (CAA) was determined in cortical and leptomeningeal blood vessels. Comparisons were made between FAD mutations and APOE4 status, with associations between pathology, clinical and genetic data investigated. In this cohort, possession of an APOE4 allele was associated with increased disease duration but not with age at onset, after adjusting for mutation sub-group and sex. We found Aβ pathology to be heterogeneous between cases although Aβ load was highest in cortical layer 3 for all mutation groups and a higher Aβ load was associated with APOE4. The PSEN1 post-codon 200 group had a higher Aβ load in lower cortical layers, with a small number of this group having increased cotton wool plaque pathology in lower layers. Cotton wool plaque frequency was positively associated with the severity of CAA in the whole cohort and in the PSEN1 post-codon 200 group. Carriers of the same PSEN1 mutation can have differing patterns of Aβ deposition, potentially because of differences in risk factors. Our results highlight possible influences of APOE4 genotype, and PSEN1 mutation type on Aβ deposition, which may have effects on the clinical heterogeneity of FAD.

Published
2021

50. Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT

Author

Sposito, Teresa, Preza, Elisavet, Mahoney, Colin J., Setó-Salvia, Núria, Ryan, Natalie S., Morris, Huw R., Arber, Charles, Devine, Michael J., Houlden, Henry, Warner, Thomas T., Bushell, Trevor J., Zagnoni, Michele, Kunath, Tilo, Livesey, Frederick J., Fox, Nick C., Rossor, Martin N., Hardy, John, and Wray, Selina

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results