Title: Spatial patterns of tau deposition are associated with amyloid, ApoE, sex, and cognitive decline in older adults

Abstract

The 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. We 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. We 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 cognitivemore » 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. These 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.« less

Authors:

Pereira, Joana B.  ^[1];

• Search DOE PAGES for author "Pereira, Joana B."
• Search DOE PAGES for ORCID "0000-0002-4604-2711"

Harrison, Theresa M. ^[2]; La Joie, Renaud ^[3]; Baker, Suzanne L. ^[4]; Jagust, William J. ^[5]

---

+ Show Author Affiliations

1. Karolinska Institute, Stockholm (Sweden). Care Sciences and Society. Dept. of Neurobiology. Division of Clinical Geriatrics; Lund Univ. (Sweden). Dept. of Clinical Sciences. Clinical Memory Research Unit
2. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
3. Univ. of California, Oakland, CA (United States). Memory and Aging Center
4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging
5. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging

Publication Date:

Wed Jan 08 00:00:00 EST 2020

Research Org.:

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

OSTI Identifier:

1816124

Grant/Contract Number:  

AC02-05CH11231

Resource Type:

Accepted Manuscript

Journal Name:

European Journal of Nuclear Medicine and Molecular Imaging

Additional Journal Information:

Journal Volume: 47; Journal Issue: 9; Journal ID: ISSN 1619-7070

Publisher:

Springer Nature

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Flortaucipir PET; Older adults; Amyloid; APOE; Sex; Cognitive decline