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IC‐P‐042: Influence of rare reelin variants on quantitative PET imaging and CSF phenotypes in late‐onset Alzheimer's disease
Author(s) -
Nho Kwangsik,
Kim Sungeun,
Risacher Shan L.,
Foroud Tatiana M.,
Aisen Paul S.,
Petersen Ronald C.,
Jagust William J.,
Jack Clifford R.,
Shaw Leslie M.,
Trojanowski John Q.,
Weiner Michael W.,
Green Robert C.,
Toga Arthur W.,
Greicius Michael D.,
Saykin Andrew J.
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.2015.06.062
Subject(s) - endophenotype , alzheimer's disease , single nucleotide polymorphism , genetic association , genetics , neuroimaging , missense mutation , biology , alzheimer's disease neuroimaging initiative , early onset alzheimer's disease , phenotype , medicine , disease , gene , genotype , neuroscience , cognition
APOE4 carrier status on brain metabolism is not firmly established, we set out to determine this effect taking advantage of the large ADNI sample. Methods:FDG-PET and MRI data from 162 cognitively normal elderly with known APOE genotype were obtained from the AD Neuroimaging Initiative (ADNI). In voxel-based analyses, using SPM8, FDG-PET maps were compared between APOE4 carriers and non-carriers. To validate our analysis, FDGPET from 40 non-carriers and 40 patients with AD matched by sex and age were also compared. Results:There were 103 APOE3 homozygotes (average age 71.5 years; 56% female) and 59 APOE4 carriers (APOE3/APOE4, average age 71.1 years; 55% female). None were APOE4 homozygotes. APOE4 carriers and noncarriers had similar metabolism in the AD-signature VOI. On voxel-based analyses, the two groups did not differ at the voxel p<0.01 uncorrected level. In AD patients, FDG-PET analysis showed significant bilateral glucose metabolic reductions in the posterior cingulate gyrus, precuneus, lateral parieto-temporal association cortex and infero-medial temporal lobe, compared with those in the healthy control group. Conclusions: Using standard PET methodology, a liberal statistical threshold, and a large sample size, we were unable to confirm previously reported AD-like patterns of cerebral metabolism in APOE4 carriers. It is possible that the ADNI sample may differ from samples previously studied or that any aberrant, AD-like, cerebral metabolism conferred by the APOE4 risk allele is too subtle to be detected with the current methodology.