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Subthreshold Amyloid Predicts Tau Deposition in Aging.
Leal, Stephanie L; Lockhart, Samuel N; Maass, Anne; Bell, Rachel K; Jagust, William J.
Afiliación
  • Leal SL; Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, stephanieleal@berkeley.edu.
  • Lockhart SN; Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
  • Maass A; Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.
  • Bell RK; Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
  • Jagust WJ; German Center for Neurodegenerative Diseases, Magdeburg, Germany 39120, and.
J Neurosci ; 38(19): 4482-4489, 2018 05 09.
Article en En | MEDLINE | ID: mdl-29686045
Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as "positive" or "negative" for biomarkers related to the core pathology of ß-amyloid (Aß). However, the accumulation of Aß begins slowly, years before biomarkers become abnormal. We used longitudinal [11C] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans (N = 71; mean age 75 years; 35% male). We used [18F] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample (N = 37). We found evidence for an inverted-U relationship between baseline Aß levels and Aß slope in asymptomatic older adults, suggesting a slowing of Aß accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of Aß predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of Aß increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative.SIGNIFICANCE STATEMENT The progressive nature of Alzheimer's disease (AD) necessitates the earliest possible detection of pathological or cognitive change if disease progression is to be slowed. We examined cognitively normal older adults in whom AD pathology is starting to develop, with the goal of early detection of AD pathology or cognitive changes. We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition. Further, it appears that rates of amyloid accumulation already begin to slow in preclinical AD, suggesting that it is a relatively late stage of AD progression. Thus, it is crucial to examine older adults early, before amyloid levels have saturated, to intervene to slow disease progression.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Proteínas tau / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: J Neurosci Año: 2018 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Proteínas tau / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: J Neurosci Año: 2018 Tipo del documento: Article