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O2‐09‐06: BDNF, Aβ, and cortical atrophy in preclinical Alzheimer's disease
Author(s) -
Doré Vincent,
Laws Simon M.,
Bourgeat Pierrick,
Fripp Jurgen,
Macaulay Lance,
Ames David,
Ellis Kathryn A.,
Maruff Paul,
Martins Ralph N.,
Masters Colin L.,
Salvado Olivier,
Rowe Christopher C.,
Villemagne Victor L.
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.2015.07.182
Subject(s) - atrophy , precuneus , hippocampus , medicine , alzheimer's disease , hippocampal formation , biomarker , rs6265 , neuroscience , endocrinology , pathology , psychology , brain derived neurotrophic factor , neurotrophic factors , disease , biology , cognition , psychiatry , biochemistry , receptor
has previously been analyzed in relation to APOE genotype, which is a known AD risk gene, but the age at onset of amyloid deposition has not been investigated as a dependent measure in relation to APOE. Methods: Using data for 132 participants and 335 visits from the Baltimore Longitudinal Study of Aging, we estimated the age at onset of amyloid accumulation for individuals who had elevated levels of amyloid at last visit as measured using positron emission tomography with Pittsburgh compound B. We examined the effects of the APOE ε2/ε3, ε3/ε3, and ε3/ε4 genotypes on the risk of amyloid accumulation using the Coxmodel, and their effects on the age at onset of amyloid accumulation using the accelerated failure time (AFT) model. Sex and years of education were included as covariates. Results: ε3/ε4 individuals had more than a double risk of accumulating amyloid (Cox model Hazard ratio [HR]1⁄42.36, 95% CI 1.13–4.92, p1⁄40.02) as well as a 13% earlier onset (AFT model b1⁄4-0.128, SE1⁄40.055, p1⁄40.02) compared to ε3/ε3. The estimated effects for ε2/ε3 individuals compared to ε3/ε3 did not reach significance, but were in agreement with a protective effect for the ε2 allele against amyloid, both in terms of the risk of amyloid accumulation (HR1⁄40.56, 95% CI 0.17–1.92, p1⁄40.36) and the age at onset of amyloid deposition (b1⁄40.054, SE1⁄40.079, p1⁄40.49). Neither sex nor education was significant. Using the AFT model results in conjunction with our finding that the average age at onset of amyloid accumulation is 69.3, we approximated the age at onset of amyloid accumulation as 75 for ε2/ε3 individuals, 71 for ε3/ε3, and 62 for ε3/ε4. Conclusions:APOE ε3/ε4 genotype was associated with a higher risk as well as an earlier onset of amyloid accumulation. Larger samples are needed to further elucidate the effects of APOE allele combinations on amyloid accumulation. This research was supported in part by the Intramural Research Program of NIH, National Institute on Aging.