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P3‐025: Fyn regulatory region haplotype specific expression
Author(s) -
Shao Yvonne,
Shaw McKenzie,
Leverenz James B.,
Bekris Lynn M.
Publication year - 2015
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.2015.06.891
Subject(s) - fyn , haplotype , biology , gene isoform , gene , microbiology and biotechnology , tyrosine kinase , genetics , signal transduction , allele
Background:Neuropathologic confirmation of Alzheimer’s disease (AD) is considered secure with a Braak Stage1⁄46 at autopsy, strongly supported by a Braak stage1⁄45, weakly supported by a Braak stage1⁄44, and unlikely at lesser stages. Some decedents with Braak stages of 5 or 6 at autopsy had been cognitively normal during life. Others with a Braak stage of 4 had been definitely demented. Is there an explanation for such variation in cognitive resilience or vulnerability to the brain lesions of AD? Comprehensive research protocol brain autopsies on 774 decedent participants in the HAASwho had been evaluated for cognitive impairment during life provide opportunity to address this question. Methods: The Cognitive Abilities and Screening Instrument (CASI) was administered at 2-3 year intervals between 1991-2012, during which more than 90% of the 3734 participants died. The last CASI score within 3 years of death was used as a measure of cognitive functioning in the final years of life. Brain autopsies were done on decedent participants when death was identified and legal consent obtained within 72 hours. Results: Definite cognitive impairment (CASI<60) had been present in 83% of 41 autopsied decedents with a Braak stage1⁄4 6, 50% of 98 with Braak stage 1⁄45, and 41% of 128 with Braak stage1⁄4 4. Fully normal cognitive impairment (CASI>1⁄482) had existed in none of of those with Braak stage 1⁄46, in 15% with Braak1⁄45, and 23% with Braak1⁄44. Among the 98 decedents with Braak stage1⁄45, definite cognitive impairment in the years prior to death was significantly associated with several coprevalent non-AD brain lesions and/or generalized brain atrophy, shorter interval between final examination and death, and marginally with counts of neocortical neuritic amyloid plaques. Several other factors (head size, education, occupational complexity, late life depression, heart disease, etc.) were not significantly associated with cognitive impairment in decedents with Braak stages of 4, 5, or 6. Conclusions:Among HAAS decedents with autopsy Braak scores of 4, 5, or 6 (considered independently), resilience or vulnerability to cognitive impairment or dementia in the final years of life was significantly associated with three neuropathologic factors: coprevalent non-AD brain lesions, generalized brain atrophy, and neocortical neuritic plaque counts.