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• W2009080915 abstract "A variable-length poly-T variant within intron 6 of the TOMM40 gene was found to correlate with the retrospectively determined age of Alzheimer's disease (AD) onset (Roses AD et al, 2009). TOMM40 encodes the translocase of the outer mitochondrial membrane pore subunit. Longer TOMM40 poly-T lengths (L) are associated with earlier age of AD onset than shorter TOMM40 (S) lengths. Because retrospective estimation of age of onset can be unreliable, we correlated TOMM40 genotype with prospectively determined age of onset of incident mild cognitive impairment (MCI) and AD to test the hypothesis that the TOMM40 L variant is associated with a younger age of symptomatic AD onset. Cognitively normal residents of Maricopa County age 21 years and older were recruited through local media ads into either the Arizona APOE cohort, a longitudinal study of cognitive aging or the Arizona Alzheimer's Disease Center cohort (Caselli RJ et al, 2009). The APOE-TOMM40 region was sequenced by Polymorphic DNA Technologies (Alameda, CA). TOMM40 poly-T lengths were converted to genotypes: short poly-T (14-20 T residues) = S, and long poly-T (≥21 T residues) = L. Symptom surveys, neurologic exams, and neuropsychological tests were repeated every 1-2 years. MCI and AD diagnoses met published diagnostic criteria. Of 37 incident cases of MCI and AD, DNA was available and sequenced in 30. Mean age of neuropsychologically confirmed symptomatic onset was 77.3 +/- 10.6 years that occurred 58.9 +/- 40.5 months after study entry. Incident MCI and AD subjects included 7 APOE e4/4's (all TOMM40 LL's, onset age 69 ± 6),10 APOE e3/4's (6 LL's, 4 SL's, onset ages 73 ± 9 and 84 ± 4), 11 APOE e3/3's (3 LL's, 8 SL's, onset ages 79 ± 18 and 83 ± 11 at clinical onset), and 2 APOE e2/3's (1 LL, 1 SL, onset ages 90 and 77). As predicted, LL's had a younger mean age at clinical onset than SL's in the overall group (73 ± 11 vs. 82 ± 9 years, p = 0.02). Additional cases are needed to test the association in APOE subgroups. The LL TOMM40 genotype was associated with younger age of incident MCI and AD onset compared to the SL genotype. A larger confirmatory study is underway." @default.
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• W2009080915 date "2010-07-01" @default.
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• W2009080915 title "P1-096: TOMM40, APOE, and age of onset of Alzheimer's disease" @default.
• W2009080915 doi "https://doi.org/10.1016/j.jalz.2010.05.644" @default.
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