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Neuropathologic features of TOMM40 '523 variant on late‐life cognitive decline
Author(s) -
Yu Lei,
Lutz Michael W.,
Farfel Jose M.,
Wilson Robert S.,
Burns Daniel K.,
Saunders Ann M.,
De Jager Philip L.,
Barnes Lisa L.,
Schneider Julie A.,
Bennett David A.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.05.002
Subject(s) - cognitive decline , genotype , cognition , genotyping , medicine , gerontology , psychology , pathology , biology , dementia , disease , genetics , psychiatry , gene
The study investigated the role of neuropathologies in the relationship between TOMM40 '523 genotype and late‐life cognitive decline. Methods Participants were community‐dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies. Results Relative to ε3/ε3 homozygotes with '523‐S/VL or '523‐VL/VL genotype, both '523‐L carriers and ε3/ε3 homozygotes with '523‐S/S genotype had faster cognitive decline. The association of '523‐L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523‐S/S was unchanged. Discussion There are two distinct TOMM40 '523 signals in relation to late‐life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.