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Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease
Author(s) -
Morgen Katrin,
Ramirez Alfredo,
Frölich Lutz,
Tost Heike,
Plichta Michael M.,
Kölsch Heike,
Rakebrandt Fabian,
Rienhoff Otto,
Jessen Frank,
Peters Oliver,
Jahn Holger,
Luckhaus Christian,
Hüll Michael,
Gertz HermannJosef,
Schröder Johannes,
Hampel Harald,
Teipel Stefan J.,
Pantel Johannes,
Heuser Isabella,
Wiltfang Jens,
Rüther Eckart,
Kornhuber Johannes,
Maier Wolfgang,
MeyerLindenberg Andreas
Publication year - 2014
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.2013.11.001
Subject(s) - apolipoprotein e , allele , dementia , genotype , alzheimer's disease , genome wide association study , medicine , neuroscience , biology , genetics , disease , single nucleotide polymorphism , gene
Background Evidence has emerged indicating that the ε4 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 ε4 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 ε4 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 ε4 carriers.