A promoter polymorphism in the monoamine oxidase A gene is associated with the pineal MAOA activity in Alzheimer's disease patients

TY - JOUR

T1 - A promoter polymorphism in the monoamine oxidase A gene is associated with the pineal MAOA activity in Alzheimer's disease patients

AU - Wu, Ying-Hui

AU - Fischer, David F

AU - Swaab, Dick F

PY - 2007/9/5

Y1 - 2007/9/5

N2 - BACKGROUND: Monoamine oxidase A (MAOA) is involved in the pathogenesis of mood disorders and Alzheimer's disease (AD). MAOA activity and gene expression have been found to be up-regulated in different brain areas of AD patients, including the pineal gland. Increased pineal MAOA activity might contribute to the reduced pineal melatonin production in AD. A promoter polymorphism of a variable number tandem repeats (VNTR) in the MAOA gene shows to affect MAOA transcriptional activity in vitro.METHODS: Here we examined in 63 aged controls and 44 AD patients the effects of the MAOA-VNTR on MAOA gene expression and activity in the pineal gland as endophenotypes, and on melatonin production.RESULTS: AD patients carrying long MAOA-VNTR genotype (consisting of 3.5- or 4-repeat alleles) showed higher MAOA gene expression and activity than the short-genotyped (i.e., 3-repeat allele) AD patients. Moreover, the AD-related up-regulation of MAOA showed up only among long-genotype bearing subjects. There was no significant effect of the MAOA-VNTR on MAOA activity or gene expression in controls, or on melatonin production in both controls and AD patients.CONCLUSION: Our data suggest that the MAOA-VNTR affects the activity and gene expression of MAOA in the brain of AD patients, and is involved in the changes of monoamine metabolism.

AB - BACKGROUND: Monoamine oxidase A (MAOA) is involved in the pathogenesis of mood disorders and Alzheimer's disease (AD). MAOA activity and gene expression have been found to be up-regulated in different brain areas of AD patients, including the pineal gland. Increased pineal MAOA activity might contribute to the reduced pineal melatonin production in AD. A promoter polymorphism of a variable number tandem repeats (VNTR) in the MAOA gene shows to affect MAOA transcriptional activity in vitro.METHODS: Here we examined in 63 aged controls and 44 AD patients the effects of the MAOA-VNTR on MAOA gene expression and activity in the pineal gland as endophenotypes, and on melatonin production.RESULTS: AD patients carrying long MAOA-VNTR genotype (consisting of 3.5- or 4-repeat alleles) showed higher MAOA gene expression and activity than the short-genotyped (i.e., 3-repeat allele) AD patients. Moreover, the AD-related up-regulation of MAOA showed up only among long-genotype bearing subjects. There was no significant effect of the MAOA-VNTR on MAOA activity or gene expression in controls, or on melatonin production in both controls and AD patients.CONCLUSION: Our data suggest that the MAOA-VNTR affects the activity and gene expression of MAOA in the brain of AD patients, and is involved in the changes of monoamine metabolism.

KW - Aged

KW - Alzheimer Disease/enzymology

KW - Biogenic Monoamines/metabolism

KW - DNA Mutational Analysis

KW - Female

KW - Gene Expression Regulation, Enzymologic/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Genetic Testing

KW - Genotype

KW - Humans

KW - Male

KW - Melatonin/biosynthesis

KW - Monoamine Oxidase/genetics

KW - Pineal Gland/enzymology

KW - Polymorphism, Genetic/genetics

KW - Promoter Regions, Genetic/genetics

KW - Up-Regulation/genetics

U2 - 10.1016/j.brainres.2007.06.053

DO - 10.1016/j.brainres.2007.06.053

M3 - Article

C2 - 17692293

SN - 0006-8993

VL - 1167

SP - 13

EP - 19

JO - Brain Research

JF - Brain Research

ER -