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P‐106: Gender, age, and APOE genotype effects on CSF Aβ 42 in cognitively normal adults
Author(s) -
Peskind Elaine R.,
Li Gail,
Petrie Eric C.,
Leverenz James B.,
Raskind Murray A.,
Galasko Douglas
Publication year - 2007
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.2007.04.170
Subject(s) - apolipoprotein e , medicine , genotype , allele , endocrinology , demography , psychology , disease , biology , genetics , sociology , gene
Background: Neurodegenerative changes of Alzheimer’s disease (AD) may begin many years prior to clinical manifestations, and women have an increased risk of AD compared to men. We recently showed that CSF levels of A 42, a sensitive AD biomarker, are significantly lower in cognitively normal apolipoprotein E*4 (APOE*E) allele carriers vs. noncarriers starting as early as 50-60 years of age. Objective: Here we examined gender effects on this relationship. Methods: Subjects were 184 cognitively normal persons aged 21-88. CSF A 42 was measured by sandwich ELISA. APOE genotype was determined. The relationship among A 42, age, gender and APOE genotype was examined using a linear regression model. Age was modeled as an orthogonal quadratic polynomial to separate our linear from quadratic trends in the A 42-age relationship. Results: Among APOE*4 allele carriers, CSF A 42 levels in women remained stable until the early postmenopausal period (age 55-60) and then declined sharply, while in male APOE*4 allele carriers, CSFA 42 levels declined linearly from age 21 (age X gender interaction p 0.007), with the relationship between age and A 42 being mainly negative and linear for men, but quadratic for women. In APOE*4 negative subjects, the A 42-age curve was not significantly different between genders—there was no significant interaction between age and gender (p 0.2) and no difference in mean A 42 levels between genders (p 0.2). Conclusions: Preclinical neuropathologic changes associated with AD may begin later (after menopause) in women compared to men, suggesting a possible protective effect of estrogen against A 42 deposition in women.