Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease
Copyright policy )Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease
AbstractBackgroundEvidence 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.MethodsThe 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.ResultsThere 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.ConclusionsThe 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.
- Düsseldorf University Hospital Germany
- University of Erlangen-Nuremberg Germany
- German Center for Neurodegenerative Diseases Germany
- Goethe University Frankfurt Germany
- University of Rostock Germany
Male, psychology [Alzheimer Disease], Genotyping Techniques, Medizin, genetics [Alzheimer Disease], genetics [Monomeric Clathrin Assembly Proteins], genetics [Cognition Disorders], Neuropsychological Tests, physiopathology [Alzheimer Disease], Polymorphism, Single Nucleotide, pathology [Alzheimer Disease], Apolipoproteins E, pathology [Brain], Alzheimer Disease, Humans, Genetic Predisposition to Disease, PICALM protein, human, Aged, Brain, Organ Size, Magnetic Resonance Imaging, Phenotype, physiopathology [Cognition Disorders], Monomeric Clathrin Assembly Proteins, genetics [Apolipoproteins E], pathology [Cognition Disorders], Female, Atrophy, Cognition Disorders, ddc: ddc:610
Male, psychology [Alzheimer Disease], Genotyping Techniques, Medizin, genetics [Alzheimer Disease], genetics [Monomeric Clathrin Assembly Proteins], genetics [Cognition Disorders], Neuropsychological Tests, physiopathology [Alzheimer Disease], Polymorphism, Single Nucleotide, pathology [Alzheimer Disease], Apolipoproteins E, pathology [Brain], Alzheimer Disease, Humans, Genetic Predisposition to Disease, PICALM protein, human, Aged, Brain, Organ Size, Magnetic Resonance Imaging, Phenotype, physiopathology [Cognition Disorders], Monomeric Clathrin Assembly Proteins, genetics [Apolipoproteins E], pathology [Cognition Disorders], Female, Atrophy, Cognition Disorders, ddc: ddc:610
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