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IC‐P‐142: Imaging genetics of SPON1 gene variant rs11023139 in Alzheimer's disease
Author(s) -
Nho Kwangsik,
Kim Sungeun,
Risacher Shan,
Shen Li,
Sherva Richard,
Green Robert,
Weiner Michael,
Saykin Andrew
Publication year - 2013
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.2013.05.139
Subject(s) - endophenotype , alzheimer's disease neuroimaging initiative , entorhinal cortex , genome wide association study , neuroimaging , quantitative trait locus , medicine , neurodegeneration , alzheimer's disease , neuroscience , psychology , oncology , hippocampus , disease , biology , genetics , cognition , single nucleotide polymorphism , gene , genotype
dependent and Ab -independent.We aimed to investigate the effects of APOE genotype on regional cerebral glucose metabolism in cognitively normal (CN) elderly. We further tried to elucidate whether or not such effects are mediated by Ab deposition.Methods: Thirty-two CN elderly participants underwent clinical examination, a range of neuropsychological tests, APOE genotyping, and Pittsburgh compound-Band fluorodeoxyglucose-PET scans.Participants with APOE genotype ε3/ε4 and ε4/ε4 were grouped as APOE ε4 carriers and genotypes ε2/ε2; ε2/ε3 andε3/ε3 were grouped as APOE ε4 non-carriers. Results: Seventeen APOE ε4 carriers and 15 non-carriers were included. Both hypometabolic and hypermetabolic regions were observed in ε4 carriers compared to non-carriers when age, education and gender were controlled. When the degree of global cerebral Ab deposition was adjusted, the hypometabolic regions in the temporo-parietal and precuneus areas (i.e., BA 22, 19 and 40) largely disappeared whereas the hypermetabolic regions persisted in medial frontal and anterior temporal areas (i.e., BA 38, 11 and 39). Similar patterns were observed when using only those subjects identified as PiB-negative. Behaviorally, verbal episodic memory scores of ε4 carriers were lower than those of non-carriers, though still within normal range.Conclusions:Our findings indicate that decreased cerebral glucose metabolism in the temporo-parietal junction and precuneus regions associated with APOE ε4 in CN appears to be mediated by Ab deposition, while the effect of APOE ε4 on hypermetabolism in frontal and anterior temporal regions is independent of Ab and may be associated with presence of compensatory mechanism in CN elderly with ε4 allele.Our findings expand on previous reports on the relationship between APOE ε4 and cerebral glucose metabolism in cognitively healthy older adults and also highlight the importance of considering hypermetabolic pattern as a biomarker for early detection of neurodegenerative disease.