Polymorphism in the BACE gene influences the risk for Alzheimer's disease.
Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase. Variations of the BACE gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different BACE polymorphisms with AD. BACE exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by BACE genotype. It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels.
Kirschling
Chartika M
CM
Department of Psychiatry, University of Bonn, Germany.
Kölsch
Heike
H
Frahnert
Christine
C
Rao
Marie Luise
ML
Maier
Wolfgang
W
Heun
Reinhard
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D016009:Chi-Square Distribution; D010450:Endopeptidases; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D010446:Peptide Fragments; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human