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P4‐285: Genetic variants at MS4A4A, DNMT3B, IL1B, TOMM40, APOE and CLU related with CSF biomarkers among Finnish patients with Alzheimer's disease
Author(s) -
EliasSonnenschein Lyzel,
Helisalmi Seppo,
Hall Anette,
Paajanen Teemu,
Laitinen Marjo,
Herukka SannaKaisa,
Rutten Bart,
Verhey Frans R.J.,
Visser Pieter Jelle,
Soininen Hilkka,
Hiltunen Mikko
Publication year - 2012
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.2013.08.066
Subject(s) - single nucleotide polymorphism , apolipoprotein e , medicine , genotyping , genome wide association study , genotype , genetics , disease , oncology , gene , biology
the epistasis between alleles of these two genes with respect to fibrillar amyloid-b (Ab) burden in cognitively normal elderly individuals. Methods: Dynamic Pittsburgh compound B positron emission tomography (PIB PET) scans, the Logan method and statistical parametric mapping were used to characterize and compare cerebral-to-cerebellar distribution volume ratios (DVR), reflecting fibrillar Aß burden in 56 cognitively normal persons (mean age, 64 years) with a reported family history of AD. Participants were divided in groups and subgroups with respect to their APOE (E 4 carriers vs. non-carriers) and BDNF (MET carriers vs. non-carriers) genotypes. Results: As we and others have previously shown, significantly higher Aß deposition (p<0.005) was found in carriers of E 4 allele (n1⁄4 33) compared to non-carriers (n 1⁄4 23) in frontal, temporal, posterior cingulate-precuneus, parietal cortices, and basal ganglia. MET carriers (n 1⁄4 23) showed no significant increase in Aß deposition in any regions when compared to non-carriers (n1⁄433), without sub-grouping with respect to the APOE genotype. Within APOE-E 4 carriers, however, MET carriers showed significantly increased Aß deposition (p<0.005) in frontal, medial temporal, lateral parietal and occipital cortices compared to non-carriers. By contrast, no significant MET effect was found in APOE-E 4 non-carriers. Conclusions: This preliminary study suggests an epistatic effect between MET BDNF and APOE-E 4 with regards to amyloid deposition in cognitively normal elderly adults. Whereas APOE-E 4 remains a prominent risk factor for LOAD with a significant effect on Aß deposition, MET BDNF seems to act as an "enhancer" of APOE-E 4 related Aß deposition in the brain. Additional studies are needed to confirm these findings, clarify the mechanisms underlying their interaction and the biological processes implicated.