Abstract
Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.
Highlights
: rs1128503), G2677T/A in exon 21 and C3435T in exon 26 [5]
It is known that the ATP-Binding Cassette Subfamily B member 1 (ABCB1) gene is highly polymorphic [4]
ABCB1 haplotypes composed of different Single Nucleotide Polymorphisms (SNPs) may better represent changes in P-gp function [4]
Summary
P-glycoprotein (P-gp), a 170 kDa membrane bound efflux pump at the apical membrane of endothelial cells, functions as part of the blood brain barrier (BBB) [1,2] and is expressed at the blood-cerebrospinal fluid (BCSF) barrier, formed by the choroid plexus [3]. POP = Population, AD = Alzheimer's Disease, VaD = Vascular Dementia, OD = Other dementias, MCI = Mild Cognitive Impairment, SD = Standard Deviation, IQR = Inter Quartile Range, MMSE = Mini Mental State Examination, CAU = Caucasian race, SNP = Single Nucleotide Polymorphism. No statistical differences were observed for genotype data, allele frequencies and haplotype data between patients with dementia and agematched controls, nor between patients with different types of dementia and age-matched controls. This could point out that ABCB1 SNPs and/or haplotypes are not related to P-gp function at the BBB This first study on ABCB1 genotypes in dementia has 27% power to detect differences in C3435T genotypes between AD and control patients. Our study suggests that frequencies of ABCB1 genotypes and haplotypes are not significantly different between demented patients and age-matched control subjects and are presently not useful as biomarker for (different types of) dementia
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