Search

Your search keyword '"Carlsson, Cynthia"' showing total 1,562 results
Start Over Author "Carlsson, Cynthia"
1,562 results on '"Carlsson, Cynthia"'

1. Older adults at greater risk for Alzheimers disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

Author

Lui, Kitty, Dave, Abhishek, Sprecher, Kate, Chappel-Farley, Miranda, Riedner, Brady, Heston, Margo, Taylor, Chase, Carlsson, Cynthia, Okonkwo, Ozioma, Asthana, Sanjay, Johnson, Sterling, Bendlin, Barbara, Benca, Ruth, and Mander, Bryce

Subjects
Humans, Female, Male, Alzheimer Disease, Middle Aged, Sleep, REM, Aged, Sleep Apnea, Obstructive, Polysomnography, Risk Factors, Verbal Learning, Apolipoprotein E4, Memory, Severity of Illness Index, Sleep Apnea Syndromes
Abstract

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimers disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Published
2024

2. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease

Author

Xicota, Laura, Cosentino, Stephanie, Vardarajan, Badri, Mayeux, Richard, Perls, Thomas T, Andersen, Stacy L, Zmuda, Joseph M, Thyagarajan, Bharat, Yashin, Anatoli, Wojczynski, Mary K, Krinsky‐McHale, Sharon, Handen, Benjamin L, Christian, Bradley T, Head, Elizabeth, Mapstone, Mark E, Schupf, Nicole, Lee, Joseph H, Barral, Sandra, Study, the Long‐Life Family, Abner, Erin, Adams, Perrie M, Aguirre, Alyssa, Albert, Marilyn S, Albin, Roger L, Allen, Mariet, Alvarez, Lisa, Andrews, Howard, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Ayres, Gayle, Barber, Robert C, Barnes, Lisa L, Bartlett, Jackie, Beach, Thomas G, Becker, James T, Beecham, Gary W, Benchek, Penelope, Bennett, David A, Bertelson, John, Biber, Sarah A, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Brewer, James B, Burke, James R, Burns, Jeffrey M, Bush, William S, Buxbaum, Joseph D, Byrd, Goldie, Cantwell, Laura B, Cao, Chuanhai, Carlsson, Cynthia M, Carrasquillo, Minerva M, Chan, Kwun C, Chasse, Scott, Chen, Yen‐Chi, Chesselet, Marie‐Francoise, Chin, Nathaniel A, Chui, Helena C, Chung, Jaeyoon, Craft, Suzanne, Crane, Paul K, Cranney, Marissa, Cruchaga, Carlos, Cuccaro, Michael L, Culhane, Jessica, Cullum, C Munro, Darby, Eveleen, Davis, Barbara, De Jager, Philip L, DeCarli, Charles, DeToledo, John C, Dickson, Dennis W, Dobbins, Nic, Duara, Ranjan, Ertekin‐Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fairchild, Thomas J, Fallin, Daniele, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Farrell, John, Farrer, Lindsay A, Fernandez‐Hernandez, Victoria, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gamboa, Adriana, Gauthreaux, Kathryn M, Gefen, Tamar, Geschwind, Daniel H, Ghetti, Bernardino, and Gilbert, John R

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Dementia, Alzheimer's Disease, Human Genome, Biotechnology, Aging, Genetics, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Alzheimer Disease, Amyloid beta-Peptides, Genetic Predisposition to Disease, Genome-Wide Association Study, Microtubule-Associated Proteins, Polymorphism, Single Nucleotide, Sequence Analysis, genetic risk, late-onset Alzheimer's disease, microtubule protein, MTUS2 gene, whole genome sequence, Long‐Life Family Study, Alzheimer's Disease Genetic Consortium, Alzheimer's Biomarkers Consortium‐Down Syndrome, late‐onset Alzheimer's disease, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionLate-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.MethodsWe conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aβ) levels.ResultsWe identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10-9). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aβ42/40 ratio compared to lower amyloid.DiscussionMTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology.HighlightsLong-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.

Published
2024

5. Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity.

Author

Mander, Bryce A, Dave, Abhishek, Lui, Kitty K, Sprecher, Katherine E, Berisha, Destiny, Chappel-Farley, Miranda G, Chen, Ivy Y, Riedner, Brady A, Heston, Margo, Suridjan, Ivonne, Kollmorgen, Gwendlyn, Zetterberg, Henrik, Blennow, Kaj, Carlsson, Cynthia M, Okonkwo, Ozioma C, Asthana, Sanjay, Johnson, Sterling C, Bendlin, Barbara B, and Benca, Ruth M

Subjects
Aging, Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Genetics, Neurosciences, Sleep Research, Dementia, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Cognitive Dysfunction, Female, Humans, Inflammation, Male, Middle Aged, Peptide Fragments, Sleep, tau Proteins, Alzheimer's disease, sleep spindles, tau phosphorylation, inflammation, neurodegeneration, memory, Alzheimer’s disease, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Study objectivesFast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD.MethodsFifty-eight cognitively unimpaired, β-amyloid-negative, older adults (mean ± SD; 61.4 ± 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, β-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to

Published
2022

7. Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer's Disease.

Author

Gaitán, Julian M, Asthana, Sanjay, Carlsson, Cynthia M, Engelman, Corinne D, Johnson, Sterling C, Sager, Mark A, Wang, Dan, Dubal, Dena B, and Okonkwo, Ozioma C

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Prevention, Brain Disorders, Genetics, Acquired Cognitive Impairment, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, Female, Humans, Male, Alzheimer Disease, Neurodegenerative Diseases, Glucuronidase, Heterozygote, Hormones, Alzheimer's disease, cerebrospinal fluid, KL-VS, Klotho, serum, Alzheimer’s disease, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundKlotho is a longevity and neuroprotective hormone encoded by the KLOTHO gene, and heterozygosity for the KL-VS variant confers a protective effect against neurodegenerative disease.ObjectiveTest whether klotho concentrations in serum or cerebrospinal fluid (CSF) vary as a function of KLOTHO KL-VS genotype, determine whether circulating klotho concentrations from serum and CSF differ from one another, and evaluate whether klotho levels are associated with Alzheimer's disease risk factors.MethodsCirculating klotho was measured in serum (n = 1,116) and CSF (n = 183) of cognitively intact participants (aged 62.4 ± 6.5 years; 69.5% female). KLOTHO KL-VS zygosity (non-carrier; heterozygote; homozygote) was also determined. Linear regression was used to test whether klotho hormone concentration varied as a function of KL-VS genotype, specimen source, and demographic and clinical characteristics.ResultsSerum and CSF klotho were higher in KL-VS carriers than non-carriers. Klotho concentration was higher in CSF than in serum. Females had higher serum and CSF klotho, while younger age was associated with higher klotho in CSF.ConclusionIn a cohort enriched for risk for Alzheimer's disease, heterozygotic and homozygotic carriers of the KL-VS allele, females, and younger individuals have higher circulating klotho. Fluid source, KL-VS genotype, age, and sex should be considered in analyses of circulating klotho on brain health.

Published
2022

8. AD‐associated CSF biomolecular changes are attenuated in KL‐VS heterozygotes

Author

Driscoll, Ira, Ma, Yue, Lose, Sarah R, Gallagher, Catherine L, Johnson, Sterling C, Asthana, Sanjay, Hermann, Bruce P, Sager, Mark A, Blennow, Kaj, Zetterberg, Henrik, Carlsson, Cynthia M, Engelman, Corinne D, Dubal, Dena B, and Okonkwo, Ozioma C

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Acquired Cognitive Impairment, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Behavioral and Social Science, Basic Behavioral and Social Science, Neurodegenerative, Prevention, Dementia, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Alzheimer's disease, CSF, biomarkers, memory, executive function, tau, Genetics, Biological psychology
Abstract

IntroductionDementia as an inevitable aging consequence has been challenged and underscores the need for investigations of the factors that confer resilience. We examine whether the functionally advantageous KL-VS variant of the putative aging suppressor KLOTHO gene attenuates age-related cognitive decline and deleterious biomolecular changes.MethodsTrajectories of change in memory and executive function (N = 360; 2-12 visits) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers-amyloid beta (Aβ)42, total tau (t-tau), phosphorylated tau (p-tau) (N = 112; 2-4 samplings)-were compared between KL-VS non-carriers and heterozygotes in middle-aged and older adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center studies.ResultsMemory and executive function declined (p's ≤ 0.001) and CSF t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42 levels increased (all p's ≤ 0.004) with age. The rate of p-tau accumulation was attenuated for KL-VS heterozygotes (p = 0.03).DiscussionKL-VS heterozygosity may confer resilience to AD-associated biomolecular changes.

Published
2022

9. Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment

Author

Hale, Madeline R., Langhough, Rebecca, Du, Lianlian, Hermann, Bruce P., Van Hulle, Carol A., Carboni, Margherita, Kollmorgen, Gwendlyn, Basche, Kristin E., Bruno, Davide, Sanson-Miles, Leah, Jonaitis, Erin M., Chin, Nathaniel A., Okonkwo, Ozioma C., Bendlin, Barbara B., Carlsson, Cynthia M., Zetterberg, Henrik, Blennow, Kaj, Betthauser, Tobey J., Johnson, Sterling C., and Mueller, Kimberly D.

Published
2024
Full Text
View/download PDF

11. Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status

Author

Gallagher, Rigina L., Koscik, Rebecca Langhough, Moody, Jason F., Vogt, Nicholas M., Adluru, Nagesh, Kecskemeti, Steven R., Van Hulle, Carol A., Chin, Nathaniel A., Asthana, Sanjay, Kollmorgen, Gwendlyn, Suridjan, Ivonne, Carlsson, Cynthia M., Johnson, Sterling C., Dean, III, Douglas C., Zetterberg, Henrik, Blennow, Kaj, Alexander, Andrew L., and Bendlin, Barbara B.

Published
2023
Full Text
View/download PDF

13. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
Full Text
View/download PDF

18. Amyloid-β positivity is less prevalent in cognitively unimpaired KLOTHO KL-VS heterozygotes.

Author

Cook, Noah, Driscoll, Ira, Gaitán, Julian M, Glittenberg, Matthew, Betthauser, Tobey J, Carlsson, Cynthia M, Johnson, Sterling C, Asthana, Sanjay, Zetterberg, Henrik, Blennow, Kaj, Kollmorgen, Gwendlyn, Quijano-Rubio, Clara, Dubal, Dena B, and Okonkwo, Ozioma C

Abstract

Background: Klotho, encoded by the KLOTHO gene, is an anti-aging and neuroprotective protein. KLOTHO KL-VS heterozygosity (KL-VSHET) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau). Objective: We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk. Methods: The sample consisted of 704 cognitively unimpaired, late middle-aged, and older adults; MeanAge(SD) = 64.9(8.3). Serum klotho was available for a sub-sample of 396 participants; MeanAge(SD) = 66.8(7.4). Covariate-adjusted logistic regression examined whether A + or T+, and multinomial regression examined whether A/T status, vary by KL-VS genotype. Covariate-adjusted linear regression examined whether serum klotho levels differ based on A+, T+, or A/T status. Results: A+ prevalence was lower in KL-VSHET (p = 0.05), with no differences in T + prevalence (p = 0.52). KL-VSHET also had marginally lower odds of being A + T- (p = 0.07). Serum klotho levels did not differ based on A+, T+, or A/T status (all ps ≥ 0.40). Conclusions: KL-VSHET is associated with lower odds of being positive for Aβ, regardless of whether one is also positive for tau. Conversely, the likelihood of being tau positive did not differ based on KL-VS genotype. Our findings add to the growing KLOTHO literature and suggests the need for further research focused on understanding the mechanisms underlying KL-VS-related putative resilience to AD. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

19. Post‐GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3

Author

Panyard, Daniel J., primary, Reus, Lianne M., additional, Ali, Muhammad, additional, Liu, Jihua, additional, Deming, Yuetiva K., additional, Lu, Qiongshi, additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Wild, Norbert, additional, Visser, Pieter J., additional, Bertram, Lars, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Gobom, Johan, additional, Western, Dan, additional, Sung, Yun Ju, additional, Carlsson, Cynthia M., additional, Johnson, Sterling C., additional, Asthana, Sanjay, additional, Cruchaga, Carlos, additional, Tijms, Betty M., additional, Engelman, Corinne D., additional, and Snyder, Michael P., additional

Published
2024
Full Text
View/download PDF

21. Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers

Author

Casaletto, Kaitlin B, Elahi, Fanny M, Bettcher, Brianne M, Neuhaus, John, Bendlin, Barbara B, Asthana, Sanjay, Johnson, Sterling C, Yaffe, Kristine, Carlsson, Cynthia, Blennow, Kaj, Zetterberg, Henrik, and Kramer, Joel H

Subjects
Alzheimer's Disease, Dementia, Brain Disorders, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Neurosciences, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoproteins E, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Imaging, Three-Dimensional, Independent Living, Magnetic Resonance Imaging, Male, Memory Disorders, Mental Recall, Middle Aged, Neurogranin, Neuropsychological Tests, Peptide Fragments, tau Proteins, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults.MethodsWe analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers).ResultsHigher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes (p < 0.03), but not with CSF Aβ42 (p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations (p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores (p > 0.40), and did not interact with neurogranin to predict memory (p > 0.10).ConclusionsSynaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions.

Published
2017

22. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults

Author

Sprecher, Kate E, Koscik, Rebecca L, Carlsson, Cynthia M, Zetterberg, Henrik, Blennow, Kaj, Okonkwo, Ozioma C, Sager, Mark A, Asthana, Sanjay, Johnson, Sterling C, Benca, Ruth M, and Bendlin, Barbara B

Subjects
Acquired Cognitive Impairment, Sleep Research, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Prevention, Clinical Research, Dementia, Aging, Alzheimer's Disease, Brain Disorders, Neurodegenerative, Neurological, Amyloid beta-Peptides, Biomarkers, Chemokine CCL2, Chitinase-3-Like Protein 1, Female, Humans, Longitudinal Studies, Male, Mental Status Schedule, Middle Aged, Neurofilament Proteins, Nuclear Proteins, Peptide Fragments, Phosphorylation, RNA-Binding Proteins, Self Report, Sleep, Sleep Wake Disorders, tau Proteins, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.MethodsWe investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.ResultsWorse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.ConclusionsSelf-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.

Published
2017

23. Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

Author

Jun, Gyungah R, Chung, Jaeyoon, Mez, Jesse, Barber, Robert, Beecham, Gary W, Bennett, David A, Buxbaum, Joseph D, Byrd, Goldie S, Carrasquillo, Minerva M, Crane, Paul K, Cruchaga, Carlos, De Jager, Philip, Ertekin‐Taner, Nilufer, Evans, Denis, Fallin, M Danielle, Foroud, Tatiana M, Friedland, Robert P, Goate, Alison M, Graff‐Radford, Neill R, Hendrie, Hugh, Hall, Kathleen S, Hamilton‐Nelson, Kara L, Inzelberg, Rivka, Kamboh, M Ilyas, Kauwe, John SK, Kukull, Walter A, Kunkle, Brian W, Kuwano, Ryozo, Larson, Eric B, Logue, Mark W, Manly, Jennifer J, Martin, Eden R, Montine, Thomas J, Mukherjee, Shubhabrata, Naj, Adam, Reiman, Eric M, Reitz, Christiane, Sherva, Richard, St. George‐Hyslop, Peter H, Thornton, Timothy, Younkin, Steven G, Vardarajan, Badri N, Wang, Li‐San, Wendlund, Jens R, Winslow, Ashley R, Adams, Perrie M, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Barmada, Michjael M, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, De Jager, Philip L, DeCarli, Charles, DeKosky, Steven T, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Doody, Rachelle S, Duara, Ranjan, Faber, Kelley M, Fairchild, Thomas J, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Green, Robert C, and Growdon, John H

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Neurodegenerative, Brain Disorders, Human Genome, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Prevention, Biotechnology, Aging, Dementia, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Apolipoprotein E4, GTPase-Activating Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Heparin-binding EGF-like Growth Factor, Humans, Membrane Glycoproteins, Molecular Chaperones, NFI Transcription Factors, Peroxisomal Bifunctional Enzyme, Polymorphism, Single Nucleotide, Receptors, GABA, Alzheimer's Disease Genetics Consortium, APOE interaction, Alzheimer's disease, Genome-wide association, Transethnic, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionGenetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.MethodsWe conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset.ResultsGenome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P

Published
2017

24. KLOTHO KL‐VS heterozygosity is associated with diminished age‐related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.

Author

Driscoll, Ira Frahmand, Lose, Sarah, Ma, Yue, Bendlin, Barbara B., Gallagher, Catherine, Johnson, Sterling C., Asthana, Sanjay, Hermann, Bruce, Sager, Mark A., Blennow, Kaj, Zetterberg, Henrik, Carlsson, Cynthia, Kollmorgen, Gwendlyn, Quijano‐Rubio, Clara, Dubal, Dena, and Okonkwo, Ozioma C.

Abstract

INTRODUCTION: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL‐VS variant (KL‐VS heterozygosity [KL‐VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin‐6 [IL‐6], S100 calcium‐binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase‐3‐like protein 1 [YKL‐40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α‐synuclein [α‐Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]). METHODS: This Alzheimer disease risk‐enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate‐adjusted multivariate regression examined relationships between age (mean‐split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL‐VSHET (N = 122) and non‐carriers (KL‐VSNC; N = 332). RESULTS: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age‐stratified analyses, KL‐VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL‐6, S100B, Ng, and α‐Syn (Ps ≥ 0.13) in KL‐VSHET. Although age‐related differences in GFAP, sTREM2, and YKL‐40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL‐VSNC. DISCUSSION: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL‐VSHET. Highlights: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction.KLOTHO KL‐VS non‐carriers exhibit this same pattern, which is does not significantly differ between younger and older KL‐VS heterozygotes for interleukin‐6, S100 calcium‐binding protein B, neurogranin, and total α‐synuclein.Although age‐related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase‐3‐like protein 1 are evident for both KL‐VS groups, the magnitude of the effect is markedly stronger for KL‐VS non‐carriers.Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL‐VS heterozygotes. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

25. CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges

Author

Jonaitis, Erin M, primary, Jeffers, Beckie, additional, VandenLangenberg, Monica, additional, Ma, Yue, additional, Van Hulle, Carol, additional, Langhough, Rebecca, additional, Du, Lianlian, additional, Chin, Nathaniel A, additional, Przybelski, Robert J, additional, Hogan, Kirk J, additional, Christian, Bradley T, additional, Betthauser, Tobey J, additional, Okonkwo, Ozioma C, additional, Bendlin, Barbara B, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M, additional, and Johnson, Sterling C, additional

Published
2024
Full Text
View/download PDF

26. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Author

Ashton, Nicholas J., primary, Brum, Wagner S., additional, Di Molfetta, Guglielmo, additional, Benedet, Andrea L., additional, Arslan, Burak, additional, Jonaitis, Erin, additional, Langhough, Rebecca E., additional, Cody, Karly, additional, Wilson, Rachael, additional, Carlsson, Cynthia M., additional, Vanmechelen, Eugeen, additional, Montoliu-Gaya, Laia, additional, Lantero-Rodriguez, Juan, additional, Rahmouni, Nesrine, additional, Tissot, Cecile, additional, Stevenson, Jenna, additional, Servaes, Stijn, additional, Therriault, Joseph, additional, Pascoal, Tharick, additional, Lleó, Alberto, additional, Alcolea, Daniel, additional, Fortea, Juan, additional, Rosa-Neto, Pedro, additional, Johnson, Sterling, additional, Jeromin, Andreas, additional, Blennow, Kaj, additional, and Zetterberg, Henrik, additional

Published
2024
Full Text
View/download PDF

27. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Author

Cukier, Holly N, Kunkle, Brian W, Vardarajan, Badri N, Rolati, Sophie, Hamilton-Nelson, Kara L, Kohli, Martin A, Whitehead, Patrice L, Dombroski, Beth A, Van Booven, Derek, Lang, Rosalyn, Dykxhoorn, Derek M, Farrer, Lindsay A, Cuccaro, Michael L, Vance, Jeffery M, Gilbert, John R, Beecham, Gary W, Martin, Eden R, Carney, Regina M, Mayeux, Richard, Schellenberg, Gerard D, Byrd, Goldie S, Haines, Jonathan L, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barmada, M Michael, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cai, Guiqing, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlsson, Cynthia M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, Cruchaga, Carlos, De Jager, Philip L, DeCarli, Charles, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fallin, M Daniele, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Go, Rodney CP, Goate, Alison M, Graff-Radford, Neill R, Green, Robert C, Griffith, Patrick, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Haroutunian, Vahram, Harrell, Lindy E, Honig, Lawrence S, Huebinger, Ryan M, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, and Jin, Lee-Way

Subjects
Biological Sciences, Genetics, Human Genome, Neurodegenerative, Neurosciences, Dementia, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Alzheimer's Disease, Clinical Research, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Alzheimer's Disease Genetics Consortium, Clinical sciences
Abstract

ObjectiveTo identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD.MethodsCustom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families.ResultsA 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42-3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12-2.44]), and joint analysis increased the significance (p = 1.414 × 10(-5), OR = 1.81 [95% CI: 1.38-2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function.ConclusionsThis common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD.

Published
2016

28. Assessment of the genetic variance of late-onset Alzheimer's disease

Author

Ridge, Perry G, Hoyt, Kaitlyn B, Boehme, Kevin, Mukherjee, Shubhabrata, Crane, Paul K, Haines, Jonathan L, Mayeux, Richard, Farrer, Lindsay A, Pericak-Vance, Margaret A, Schellenberg, Gerard D, Kauwe, John SK, Consortium, Alzheimer's Disease Genetics, Adams, Perrie M, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barber, Robert C, Barmada, Michael M, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, Cruchaga, Carlos, De Jager, Philip L, DeCarli, Charles, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Doody, Rachelle S, Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fairchild, Thomas J, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Goate, Alison M, Graff-Radford, Neill R, Green, Robert C, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Hamilton-Nelson, Kara L, Hardy, John, Harrell, Lindy E, Honig, Lawrence S, Huebinger, Ryan M, Huentelman, Matthew J, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Jicha, Gregory A, Jin, Lee-Way, Jun, Gyungah, Kamboh, M Ilyas, Karydas, Anna, Katz, Mindy J, Kaye, Jeffrey A, Kim, Ronald, and Kowall, Neil W

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Human Genome, Acquired Cognitive Impairment, Aging, Dementia, Genetics, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Protein Precursor, Datasets as Topic, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Glycoproteins, Netrin Receptors, Polymorphism, Single Nucleotide, Receptors, Cell Surface, Receptors, Immunologic, Risk, Alzheimer's Disease Genetics Consortium, Alzheimer's disease, Genetic variance, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions.

Published
2016

30. Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer’s disease

Author

Dougherty, Ryan J., Boots, Elizabeth A., Lindheimer, Jacob B., Stegner, Aaron J., Van Riper, Stephanie, Edwards, Dorothy F., Gallagher, Catherine L., Carlsson, Cynthia M., Rowley, Howard A., Bendlin, Barbara B., Asthana, Sanjay, Hermann, Bruce P., Sager, Mark A., Johnson, Sterling C., Okonkwo, Ozioma C., and Cook, Dane B.

Published
2020
Full Text
View/download PDF

32. Measuring longitudinal cognition: Individual tests versus composites

Author

Jonaitis, Erin M., Koscik, Rebecca L., Clark, Lindsay R., Ma, Yue, Betthauser, Tobey J., Berman, Sara E., Allison, Samantha L., Mueller, Kimberly D., Hermann, Bruce P., Van Hulle, Carol A., Christian, Bradley T., Bendlin, Barbara B., Blennow, Kaj, Zetterberg, Henrik, Carlsson, Cynthia M., Asthana, Sanjay, and Johnson, Sterling C.

Published
2019
Full Text
View/download PDF

33. Association between enrollment factors and incident cognitive impairment in Blacks and Whites: Data from the Alzheimer's Disease Center

Author

Gleason, Carey E., Norton, Derek, Zuelsdorff, Megan, Benton, Susan F., Wyman, Mary F., Nystrom, Naomi, Lambrou, Nickolas, Salazar, Hector, Koscik, Rebecca L., Jonaitis, Erin, Carter, Fabu, Harris, Brieanna, Gee, Alexander, Chin, Nathaniel, Ketchum, Frederick, Johnson, Sterling C., Edwards, Dorothy F., Carlsson, Cynthia M., Kukull, Walter, and Asthana, Sanjay

Published
2019
Full Text
View/download PDF

36. The KEEPS-Cognitive and Affective Study: baseline associations between vascular risk factors and cognition.

Author

Wharton, Whitney, Gleason, Carey E, Dowling, N Maritza, Carlsson, Cynthia M, Brinton, Eliot A, Santoro, M Nanette, Neal-Perry, Genevieve, Taylor, Hugh, Naftolin, Frederick, Lobo, Rogerio A, Merriam, George, Manson, Joann E, Cedars, Marcelle I, Miller, Virginia M, Black, Dennis M, Budoff, Matthew, Hodis, Howard N, Harman, S Mitchell, and Asthana, Sanjay

Subjects
Humans, Estradiol, Hormones, Blood Glucose, Estrogens, Administration, Oral, Administration, Cutaneous, Risk Factors, Longitudinal Studies, Double-Blind Method, Attention, Cognition Disorders, Mood Disorders, Psychiatric Status Rating Scales, Neuropsychological Tests, Blood Pressure, Adult, Middle Aged, Female, Cholesterol, LDL, Cholesterol, HDL, blood pressure, clinical trial, cognition, estradiol, estrogen, hormone therapy, memory, vascular risk, Estrogen, Behavioral and Social Science, Clinical Trials and Supportive Activities, Aging, Neurosciences, Neurodegenerative, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Brain Disorders, Alzheimer's Disease, Acquired Cognitive Impairment, Prevention, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

Published
2014

37. Longitudinal trajectories of myelin loss in the context of Alzhiemer’s disease biomarkers, glial activation, and APOE4

Author

Stephenson, Henry G., primary, Kohli, Akshay, additional, Kecskemeti, Steven R, additional, Rubinski, Anna, additional, Ewers, Michael, additional, Alexander, Andrew L, additional, Deming, Yuetiva, additional, Ma, Yue, additional, Van Hulle, Carol A., additional, Langhough, Rebecca E, additional, Jonaitis, Erin M., additional, Dean, Douglas C, additional, Ulland, Tyler K., additional, Chin, Nathaniel A., additional, Okonkwo, Ozioma, additional, Betthauser, Tobey J, additional, Asthana, Sanjay, additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Wild, Norbert, additional, Carlsson, Cynthia M, additional, Johnson, Sterling C, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, and Bendlin, Barbara B, additional

Published
2023
Full Text
View/download PDF

39. Preclinical Alzheimer’s disease is associated with distinct gut microbial metagenomic profiles

Author

Kang, Jea Woo, primary, Heston, Margo B., additional, Deming, Yuetiva, additional, González, Antonio, additional, Ulland, Tyler K., additional, Johnson, Sterling C, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Chin, Nathaniel A., additional, Grover, Ethan, additional, Vemuganti, Vaibhav BV, additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Knight, Rob, additional, Kaddurah‐Daouk, Rima F., additional, Rey, Federico E., additional, and Bendlin, Barbara B, additional

Published
2023
Full Text
View/download PDF

41. The cerebrospinal fluid A‐T+ Alzheimer disease biomarker profile: prevalence and clinical relevance

Author

Eriksson, Pontus, primary, Simrén, Joel, additional, Brum, Wagner Scheeren, additional, Ennis, Gilda E., additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Langhough, Rebecca E, additional, Jonaitis, Erin M., additional, Van Hulle, Carol A., additional, Betthauser, Tobey J, additional, Carlsson, Cynthia M., additional, Asthana, Sanjay, additional, Ashton, Nicholas J., additional, Johnson, Sterling C, additional, Shaw, Leslie M., additional, Blennow, Kaj, additional, Andreasson, Ulf, additional, Bendlin, Barbara B, additional, and Zetterberg, Henrik, additional

Published
2023
Full Text
View/download PDF

42. Gut microbiome moderates the association between metabolic syndrome and the cerebrospinal fluid concentration of YKL‐40 in a cognitively unimpaired cohort

Author

Peter, Darby, primary, Heston, Margo B., additional, Ennis, Gilda E., additional, Knight, Rob, additional, Kaddurah‐Daouk, Rima F., additional, Johnson, Sterling C, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Chin, Nathaniel A., additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Ulland, Tyler K., additional, Rey, Federico E., additional, and Bendlin, Barbara B, additional

Published
2023
Full Text
View/download PDF

43. An Update on the Building Bridges Study: Examining the effects of two interventions on trust in medical researchers and research attitudes among African American participants

Author

Bouges, Shenikqua, primary, Noell, Debra, additional, Osman, Fauzia, additional, Oby, Alayna, additional, Benton, Susan Flowers, additional, Clipps, Antwon D, additional, Fischer, Barbara L., additional, Gooding, Diane C., additional, Anthony, Ruben L, additional, Carter, Fabu P., additional, Salazar, Hector, additional, Simó, Carola A. Ferrer, additional, Ennis, Gilda E., additional, Van Hulle, Carol A., additional, Zuelsdorff, Megan, additional, Wyman, Mary F., additional, Johnson, Adrienne L., additional, Lambrou, Nickolas H., additional, James, Taryn T., additional, Carlsson, Cynthia M., additional, Asthana, Sanjay, additional, and Gleason, Carey E., additional

Published
2023
Full Text
View/download PDF

44. Associations of physical activity with cerebrospinal fluid biomarkers of neurodegeneration, neuroinflammation, and Alzheimer’s disease

Author

Planalp, Elizabeth M., primary, Van Hulle, Carol A., additional, Bendlin, Barbara B, additional, Blennow, Kaj, additional, Carboni, Margherita, additional, Carlsson, Cynthia M, additional, Engelman, Corinne D., additional, Kollmorgen, Gwendlyn, additional, Ma, Yue, additional, Okonkwo, Ozioma, additional, Johnson, Sterling C, additional, Zetterberg, Henrik, additional, and Merten, Natascha, additional

Published
2023
Full Text
View/download PDF

45. A study on the sample representativeness of the Wisconsin Alzheimer’s Disease Research Center Clinical Core participants versus the Wisconsin state population

Author

Ma, Yue, primary, Pinzon, Maria C Mora, additional, Buckingham, William R., additional, Bersch, Andrew, additional, Powell, W. Ryan, additional, LeCaire, Tamara J., additional, Ennis, Gilda E., additional, Deming, Yuetiva, additional, Jonaitis, Erin M., additional, Reuter, Leah, additional, Shi, Fangfang, additional, Spalitta, Alice, additional, Wahoske, Michelle L, additional, Bevis, William B., additional, Blazel, Hanna M., additional, Chin, Nathaniel A., additional, Edwards, Dorothy F., additional, Walaszek, Art, additional, Okonkwo, Ozioma, additional, Chappell, Richard J, additional, Johnson, Sterling C, additional, Asthana, Sanjay, additional, Gleason, Carey E., additional, Kind, Amy J., additional, Bendlin, Barbara B, additional, and Carlsson, Cynthia M, additional

Published
2023
Full Text
View/download PDF

46. Relationships between KLOTHO and APOE4‐associated β‐amyloid and tau alterations across AD continuum

Author

Cook, Noah R., primary, Driscoll, Ira, additional, Gallagher, Catherine L., additional, Johnson, Sterling C, additional, Asthana, Sanjay, additional, Hermann, Bruce P, additional, Sager, Mark A., additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Carlsson, Cynthia M., additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Wang, Dan, additional, Dubal, Dena B., additional, and Okonkwo, Ozioma, additional

Published
2023
Full Text
View/download PDF

47. A comparison of word‐list and story recall tests for prediction of biomarker‐determined Alzheimer’s disease

Author

Bruno, Davide, primary, Zinkunegi, Ainara Jauregi, additional, Kollmorgen, Gwendlyn, additional, Carboni, Margherita, additional, Wild, Norbert, additional, Carlsson, Cynthia M., additional, Bendlin, Barbara B, additional, Okonkwo, Ozioma, additional, Chin, Nathaniel A., additional, Hermann, Bruce P, additional, Asthana, Sanjay, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Langhough, Rebecca E, additional, Johnson, Sterling C, additional, and Mueller, Kimberly D, additional

Published
2023
Full Text
View/download PDF

49. CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers

Author

Wilson, Rachael E, primary, Jonaitis, Erin M., additional, Langhough, Rebecca E, additional, Betthauser, Tobey J, additional, DiFilippo, Alexandra H, additional, Christian, Bradley T., additional, Okonkwo, Ozioma, additional, Bendlin, Barbara B, additional, Chin, Nathaniel A., additional, Carlsson, Cynthia M, additional, Asthana, Sanjay, additional, Johnson, Sterling C, additional, and Zetterberg, Henrik, additional

Published
2023
Full Text
View/download PDF

50. Intra‐ and post‐procedural lumbar puncture symptoms in a sample of Black/African American, American Indian/Alaska Native, and White middle age older adults

Author

Cole, Aleshia, primary, Van Hulle, Carol A., additional, Eierman, Allison C, additional, Rovner, Sarah, additional, Chin, Nathaniel A., additional, McLester‐Davis, Lauren W. Y., additional, Johnson, Sterling C, additional, Bendlin, Barbara B, additional, Okonkwo, Ozioma, additional, Gleason, Carey E., additional, Edwards, Dorothy F., additional, Asthana, Sanjay, additional, and Carlsson, Cynthia M, additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results