Association of sex and APOE ∈4 with brain tau deposition and atrophy in older adults with Alzheimer's disease

Shaozhen Yan, Chaojie Zheng, Manish D. Paranjpe, Jian Li, Tammie L.S. Benzinger, Jie Lu, Yun Zhou

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The objective of this study was to assess the association of sex and the apolipoprotein E (APOE) ∈4 allele with brain tau deposition and atrophy in older adults with Alzheimer's disease (AD) using quantitative 18F-AV-1451 positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Preprocessed 18F-AV-1451 tau PET, raw T1-weighted structural MR images, demographic information, cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 57 elderly individuals with AD were downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. An iteratively reblurred Van Cittert partial volume correction (PVC) method was applied to all preprocessed PET images. MRI images were used for PET spatial normalization and gray matter volume calculation. 18F-AV-1451 PET standardized uptake value ratio (SUVR) was calculated relative to the cerebellum gray matter. The effect of sex and APOE ∈4 status on SUVR and gray matter volume were assessed at both region of interest (ROI) and voxelwise levels. Results: Female APOE ∈4 carriers (FACs) had significant higher 18F-AV-1451 SUVRs in the lateral temporal, parietal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions, and exhibited smaller gray matter volumes in the posterior cingulate, medial temporal, inferior temporal and amygdala regions, as compared to the non-FACs (NFACs) comprised of female APOE ∈4 non-carriers, male APOE ∈4 carriers and male APOE ∈4 non-carriers. Voxelwise analysis revealed forebrain and limbic clusters with greater 18F-AV-1451 SUVRs and lower gray matter volume between FACs compared to the NFACs. Negative correlations between ROI 18F-AV-1451 SUVRs and gray matter volumes were significant after adjusting for age and years of education. Conclusions: Among elderly individuals with AD, sex modified the effects of the APOE ∈4 allele on region-specific tau deposition and gray matter volume. FACs had elevated brain region-specific tau PET SUVR and decreased gray matter volume in comparison to NFACs. The study provides a basis for the use of precision medicine in the diagnosis of AD and evaluation of therapeutics using 18F-AV-1451 PET and structural MRI.

Original languageEnglish
Pages (from-to)10563-10572
Number of pages10
JournalTheranostics
Volume10
Issue number23
DOIs
StatePublished - 2020

Keywords

  • APOE
  • Alzheimer's disease
  • Neurodegeneration
  • Sex
  • Tau PET

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