Abstract
AbstractBackgroundThe microtubule‐associated protein tau gene rs242557 variant is associated with multiple tauopathies and dementia. This study investigated whether it was correlated with brain tau‐PET uptake in non‐demented elders.MethodNinety non‐demented elders were identified from the Alzheimer's Disease Neuroimaging Initiative cohort. We compared standardized uptake value ratios of tau‐PET tracer 18F‐AV‐1451 between rs242557 variant carriers and non‐carriers in 25 regions of interest.ResultThe minor allele A was associated with increased hippocampus 18F‐AV‐1451 uptake in non‐demented elders (left: β = 0.111, Bonferroni corrected p = 0.035; right: β = 0.103, Bonferroni corrected p = 0.031). Aβ‐positive participants (left: β = 0.206, Bonferroni corrected p = 0.029; right: β = 0.198, Bonferroni corrected p = 0.035) and APOE ε4 non‐carriers (left: β = 0.140, Bonferroni corrected p = 0.006; right: β = 0.134, Bonferroni corrected p = 0.004) exhibited approximately the same findings in hippocampus.ConclusionConsidering no obvious associations in other regions, we confirmed the significant correlation of MAPT rs242557 risk variant with increased hippocampus tau deposition in non‐demented elders. With higher magnitude signals in the hippocampus that is more likely to be uniquely affected in AD, the tau PET ligand 18F‐AV‐1451 seemed to possess a specific binding property for AD‐like tau pathology.
Highlights
Variations in the microtubule-associated protein tau gene (MAPT) which encodes tau protein for microtubule stability and signal transduction, are well docu-. *Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database
We identified a significant correlation between microtubule‐associated protein tau gene (MAPT) rs242557 risk variant and increased hippocampus uptake of tau-positron emission tomography (PET) tracer 18FAV-1451 in the non-demented elders, especially in those with abnormal Aβ deposition
Www.aging‐us.com levels than those carrying the allele G, implying that rs242557 served as a functional locus whose minor allele A could promote the expression of tau aggregates in the hippocampus
Summary
*Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). The H1 haplotype has been reported to be a primary factor for the associations of MAPT with Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and pathological tau aggregates in cognitively normal elderly [1–3]. Strong associations have been found of the locus rs242557 with plasma and cerebrospinal fluid (CSF) tau levels [6, 7], but there is a lack of research on the possible correlation between neurowww.aging‐us.com imaging of pathological tau deposits and rs242557 variant. It remains insufficient using tau PET to map whether the distribution of brain tau deposition was correlated with MAPT rs242557 variant. We compared the 18F-AV-1451 binding between rs242557 variant carriers and non-carriers in a cohort of non-demented elders
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