Browsing by Author "Quiroz, Yakeel T."

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    Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study
    (Nature Research, 2020-02-03) Reiman, Eric M.; Arboleda-Velasquez, Joseph F.; Quiroz, Yakeel T.; Huentelman, Matthew J.; Beach, Thomas G.; Caselli, Richard J.; Chen, Yinghua; Su, Yi; Myers, Amanda J.; Hardy, John; Vonsattel, Jean Paul; Younkin, Steven G.; Bennett, David A.; De Jager, Philip L.; Larson, Eric B.; Crane, Paul K.; Keene, C. Dirk; Kamboh, M. Ilyas; Kofler, Julia K.; Duque, Linda; Gilbert, John R.; Gwirtsman, Harry E.; Buxbaum, Joseph D.; Dickson, Dennis W.; Frosch, Matthew P.; Ghetti, Bernardino F.; Lunetta, Kathryn L.; Wang, Li-San; Hyman, Bradley T.; Kukull, Walter A.; Foroud, Tatiana; Haines, Jonathan L.; Mayeux, Richard P.; Pericak-Vance, Margaret A.; Schneider, Julie A.; Trojanowski, John Q.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Beecham, Gary W.; Montine, Thomas J.; Jun, Gyungah R.; Alzheimer’s Disease Genetics Consortium; Pathology and Laboratory Medicine, School of Medicine
    Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease.
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    Novel avenues of tau research
    (Wiley, 2024) Sexton, Claire E.; Bitan, Gal; Bowles, Kathryn R.; Brys, Miroslaw; Buée, Luc; Bukar Maina, Mahmoud; Clelland, Claire D.; Cohen, Ann D.; Crary, John F.; Dage, Jeffrey L.; Diaz, Kristophe; Frost, Bess; Gan, Li; Goate, Alison M.; Golbe, Lawrence I.; Hansson, Oskar; Karch, Celeste M.; Kolb, Hartmuth C.; La Joie, Renaud; Lee, Suzee E.; Matallana, Diana; Miller, Bruce L.; Onyike, Chiadi U.; Quiroz, Yakeel T.; Rexach, Jessica E.; Rohrer, Jonathan D.; Rommel, Amy; Sadri-Vakili, Ghazaleh; Schindler, Suzanne E.; Schneider, Julie A.; Sperling, Reisa A.; Teunissen, Charlotte E.; Weninger, Stacie C.; Worley, Susan L.; Zheng, Hui; Carrillo, Maria C.; Neurology, School of Medicine
    Introduction: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. Methods: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. Results: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. Discussion: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
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    Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease
    (Wiley, 2023) Aguillon, David; Langella, Stephanie; Chen, Yinghua; Sanchez, Justin; Su, Yi; Vila-Castelar, Clara; Vasquez, Daniel; Zetterberg, Henrik; Hansson, Oskar; Dage, Jeffrey L.; Janelidze, Shorena; Chen, Kewei; Fox-Fuller, Joshua T.; Aduen, Paula; Martinez, Jairo E.; Garcia, Gloria; Baena, Ana; Guzman, Claudia; Johnson, Keith; Sperling, Reisa A.; Blennow, Kaj; Reiman, Eric M.; Lopera, Francisco; Quiroz, Yakeel T.; Neurology, School of Medicine
    Introduction: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. Methods: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. Results: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. Discussion: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. Highlights: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.
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    Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer’s disease
    (Wiley, 2023) Vila-Castelar, Clara; Chen, Yinghua; Langella, Stephanie; Lopera, Francisco; Zetterberg, Henrik; Hansson, Oskar; Dage, Jeffrey L.; Janelidzde, Shorena; Su, Yi; Chen, Kewei; Pluim McDowell, Celina; Martinez, Jairo E.; Ramirez-Gomez, Liliana; Garcia, Gloria; Aguillon, David; Baena, Ana; Giraldo-Chica, Margarita; Protas, Hillary D.; Ghisays, Valentina; Rios-Romenets, Silvia; Tariot, Pierre N.; Blennow, Kaj; Reiman, Eric M.; Quiroz, Yakeel T.; Neurology, School of Medicine
    Introduction: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. Methods: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. Results: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. Discussion: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. Highlights: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers.