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P1‐065: Adam10 and bace1 are localized to synaptic vesicles
Author(s) -
Winblad Bengt,
Lundgren Jolanta,
Ahmed Saheeb,
Schedin-Weiss Sophia,
Gouras Gunnar K.,
Tjernberg Lars O.,
Frykman Susanne
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.2015.06.262
Subject(s) - synaptic vesicle , adam10 , synaptophysin , amyloid precursor protein , vesicle , chemistry , amyloid precursor protein secretase , alpha secretase , synapsin i , western blot , biochemistry , synaptic augmentation , microbiology and biotechnology , synaptic plasticity , biology , alzheimer's disease , medicine , enzyme , immunology , metalloproteinase , disintegrin , membrane , immunohistochemistry , receptor , gene , disease
index, and generalized brain atrophy. Neuropathologic endpoints were dichotomized to identify the most severely affected. Analyses were by linear and logistic regression controlling for education and age at final testing, or for age at death.Results: The rs13381522SNP and ApoE ε4 were significantly and independently associated with definite cognitive impairment near the end of life, with comparable coefficients. ApoE ε4 was significantly associated with all of the AD-related brain abnormalities (except generalized brain atrophy) with Odds Ratios of 2.0-5.6. The rs13381522 SNP was associated with higher Braak Stage (OR1⁄42.99; CI1⁄41.19-7.5) and neocortical NP (OR1⁄42.64; CI1⁄41.0-6.9). Its association with neocortical NFT was marginal (OR1⁄42.07; CI1⁄40.75-5.60). The rs3764479 SNP was not associated with any endpoints, ApoE ε4, or rs13381522. Allele frequencies in this panel were 0.102 for ApoE ε4, 0.038 for rs13381522, and 0.211 for rs3764479. Conclusions: In autopsied HAAS participants, TTR rs13381522 was associated with late life cognitive impairment, Braak stage, and neocortical neuritic plaque counts at strengths similar to those for ApoE ε4. Unlike ApoE ε4, this TTR SNP was not significantly associated with diffuse plaque counts, hippocampal lesions, or CAA. The lower allele frequency of rs13381522 may have contributed to these differences. While our findings implicate TTR rs13381522 SNP as a genetic risk factor for the Alzheimer process, independent confirmation is essential.