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

Pereira, Joana B.; Harrison, Theresa M.; La Joie, Renaud; Baker, Suzanne L.; Jagust, William J.

doi:10.1007/s00259-019-04669-x

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

Journal Article · Wed Jan 08 04:00:00 EST 2020 · European Journal of Nuclear Medicine and Molecular Imaging

DOI:https://doi.org/10.1007/s00259-019-04669-x· OSTI ID:1816124

^[1]; Harrison, Theresa M. ^[2]; La Joie, Renaud ^[3]; Baker, Suzanne L. ^[4]; Jagust, William J. ^[5]

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; OSTI
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
Univ. of California, Oakland, CA (United States). Memory and Aging Center
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging
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

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 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. 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.

View Accepted Manuscript (DOE)

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

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

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1816124

Alternate ID(s):: OSTI ID: 22930329

Journal Information:: European Journal of Nuclear Medicine and Molecular Imaging, Journal Name: European Journal of Nuclear Medicine and Molecular Imaging Journal Issue: 9 Vol. 47; ISSN 1619-7070

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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