Dataset Information

Tau pathology in cognitively normal older adults.

ABSTRACT:

Introduction

Tau pathology, a hallmark of Alzheimer's disease, is observed in the brains of virtually all individuals over 70 years.

Methods

Using ¹⁸F-AV-1451 (¹⁸F-flortaucipir) positron emission tomography, we evaluated tau pathology in 54 cognitively normal participants (mean age: 77.5 years, SD: 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between positron emission tomography signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.

Results

Greater age, male sex, black race, and amyloid positivity were associated with higher ¹⁸F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (? = -1.124, SE = 0.485, P = .025) and a steeper decline in memory performance (? = -0.086, SE = 0.039, P = .029).

Discussion

Assessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer's disease.

SUBMITTER: Ziontz J

PROVIDER: S-EPMC6732758 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Tau pathology in cognitively normal older adults.

Ziontz Jacob J Bilgel Murat M Shafer Andrea T AT Moghekar Abhay A Elkins Wendy W Helphrey Jessica J Gomez Gabriela G June Danielle D McDonald Michael A MA Dannals Robert F RF Azad Babak Behnam BB Ferrucci Luigi L Wong Dean F DF Resnick Susan M SM

Alzheimer's & dementia (Amsterdam, Netherlands) 20190906

<h4>Introduction</h4>Tau pathology, a hallmark of Alzheimer's disease, is observed in the brains of virtually all individuals over 70 years.<h4>Methods</h4>Using <sup>18</sup>F-AV-1451 (<sup>18</sup>F-flortaucipir) positron emission tomography, we evaluated tau pathology in 54 cognitively normal participants (mean age: 77.5 years, SD: 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between positron emission tomography signal and age, sex, race, and amyloid positivit ...[more]

PMID: 31517026

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Project description:To improve the ability to develop treatments that prevent incipient Alzheimer disease (AD) from progressing to overt AD, it is important to understand the molecular basis of the earliest pathophysiological abnormalities and to determine how amyloid-? (A?) is involved very early in its pathogenesis.To investigate 2 specific A? oligomers, A? trimers and A?*56, in human cerebrospinal fluid (CSF); evaluate the effects of aging and AD; and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau.A CSF sampling study.The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden.Forty-eight older adults with mild cognitive impairment or AD (impaired group); 49 age-matched cognitively intact control subjects (unimpaired group); and 10 younger, normal control subjects.Measurements of CSF A? trimers, A?*56, the 42-amino acid A? isoform (A?1-42), total tau (T-tau), and phospho-tau 181 (p-tau(181)). The hypothesis being tested was formulated after data collection. RESULTS We observed that A? trimers and A?*56 levels increased with age; within the unimpaired group, they were elevated in subjects with T-tau/A?1-42 ratios greater than a cutoff that distinguished the unimpaired group from subjects with AD. In the unimpaired group, T-tau and p-tau(181) were found to correlate strongly with A? trimers and A?*56 (r > 0.63), but not with A?1-42 (-0.10 < r < -0.01). The strong correlations were found to be attenuated in the impaired group.In cognitively intact older adults, CSF A? trimers and A?*56 were elevated in individuals at risk for AD, and they showed stronger relationships with tau than did A?1-42, a surrogate for A? fibril deposition. These findings suggest that prior to overt symptoms, 1 or both of the A? oligomers, but not fibrillar A?, is coupled to tau; however, this coupling is weakened or broken when AD advances to symptomatic stages. The uncoupling is interesting in light of the failure of experimental A? therapies to improve mild cognitive impairment/AD, which has prompted a shift in the timing of A? therapies to asymptomatic subjects. Knowing which A? species to target in asymptomatic subjects may enhance the success of future treatments for AD.

Dataset Information

Tau pathology in cognitively normal older adults.

Introduction

Methods

Results

Discussion

Publications

Tau pathology in cognitively normal older adults.

Similar Datasets

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