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Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease

Item Type:Article
Title:Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease
Creators Name:Morgen, K. and Ramirez, A. and Froelich, L. and Tost, H. and Plichta, M.M. and Koelsch, H. and Rakebrandt, F. and Rienhoff, O. and Jessen, F. and Peters, O. and Jahn, H. and Luckhaus, C. and Huell, M. and Gertz, H.J. and Schroeder, J. and Hampel, H. and Teipel, S.J. and Pantel, J. and Heuser, I. and Wiltfang, J. and Ruether, E. and Kornhuber, J. and Maier, W. and Meyer-Lindenberg, A.
Abstract:BACKGROUND: Evidence has emerged indicating that the epsilon4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD. METHODS: The aim of this study was to investigate interaction effects of the APOE epsilon4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia. RESULTS: There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE epsilon4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function. CONCLUSIONS: The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE epsilon4 carriers.
Keywords:Alzheimer's Disease, PICALM, APOE, Genetic Interaction, Brain Atrophy
Source:Alzheimer's & Dementia
ISSN:1552-5260
Publisher:Elsevier (U.S.A.)
Volume:10
Number:5 Suppl
Page Range:S269-S276
Date:October 2014
Official Publication:https://doi.org/10.1016/j.jalz.2013.11.001
PubMed:View item in PubMed

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