Abstract
PurposeThe abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline.MethodsWe included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread.ResultsWe found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas.ConclusionsThese findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.
Highlights
Alzheimer’s disease (AD) is characterized by a long-lasting preclinical phase, in which the presence of progressively increasing pathology is not yet accompanied by clinical symptoms [1]
Ε3ε4 carriers showed higher PiB distribution volume ratios (DVRs) compared with both ε2ε3 (d = 1.4, p = 0.004) and ε3ε3 (d = 0.9, p < 0.001) carriers, and ε2ε3 were less educated than ε3ε3 carriers (d = 0.7, p = 0.003)
We found that women had greater tau in temporo-parietal and anterior frontal components compared with men, indicating that the effects of sex on tau deposition might be more widespread than previously thought
Summary
Alzheimer’s disease (AD) is characterized by a long-lasting preclinical phase, in which the presence of progressively increasing pathology is not yet accompanied by clinical symptoms [1]. In this preclinical phase, biomarkers of tau pathology have important prognostic value and could be used to predict cognitive decline and identify individuals at higher risk of developing AD [2]. We sought to address these issues by identifying the spatial patterns of tau in older adults and assessing whether tau in these patterns is related to amyloid, APOE, sex, or longitudinal cognitive decline. We sorted the spatial patterns based on the frequency of tau positivity across subjects to determine a proxy for regional tau spread
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