title: APBB2 genetic polymorphisms are associated with severe cognitive impairment in centenarians.
abstract: APBB2 gene encodes for β-amyloid precursor protein-binding family B member 2, (APBB2, FE65-like, FE65L1), an adaptor protein binding to the cytoplasmatic domain of β-amyloid precursor protein (βAPP). Over-expression of APBB2 promotes formation of β-amyloid (Aβ), the main constituent of senile plaques. Polymorphisms within APBB2 gene have been proposed as candidate risk factors for Alzheimer's disease. However, their association with longevity has never been investigated. Here we present the first attempt to analyze APBB2 polymorphisms in centenarians. We used a PCR-RFLP method to analyze two intronic nucleotide substitutions: hCV1558625 (rs17443013) and rs13133980. We found no differences in genotype or allele distribution between centenarians and young controls. After stratification of centenarians upon their cognitive performance, the APBB2 rs13133980 G allele was over-represented in centenarians with severe cognitive impairment compared to individuals without this disability. Also the hCV1558625-rs13133980 AG haplotype increased relative risk for severe cognitive impairment in centenarians. Our results support the concept of APBB2 polymorphism association with cognitive performance in the oldest age.
authors: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, 8/10 Czechoslowacka St., 92-216 Lodz, Poland. ewa.golanska@umed.lodz.pl
authors: Ewa
authors: E
authors: Golanska
authors: Monika
authors: M
authors: Sieruta
authors: Sylwia M
authors: SM
authors: Gresner
authors: Anna
authors: A
authors: Pfeffer
authors: Malgorzata
authors: M
authors: Chodakowska-Zebrowska
authors: Tomasz M
authors: TM
authors: Sobow
authors: Izabela
authors: I
authors: Klich
authors: Malgorzata
authors: M
authors: Mossakowska
authors: Aleksandra
authors: A
authors: Szybinska
authors: Maria
authors: M
authors: Barcikowska
authors: Pawel P
authors: PP
authors: Liberski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000369:Aged, 80 and over; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007361:Intelligence Tests; D007438:Introns; D008297:Male; D058225:Plaque, Amyloid / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales
chemical_list: C466684:APBB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor