title: Zinc transporter mRNA levels in Alzheimer's disease postmortem brain.
abstract: Zinc (Zn2+) is concentrated into pre-synaptic vesicles and co-released with neurotransmitter at some synapses. Zn2+ can accelerate assembly of the amyloid-β peptides (Aβ) and tau protein central to the neuropathological changes found in Alzheimer's disease (AD). Altered protein levels of the membrane Zn2+ transporters ZnT1, ZnT4, and ZnT6 have been reported in AD postmortem brain tissue. The present study analyzed mRNA levels of five established (LIV1, ZIP1, ZnT1, ZnT4, and ZnT6) and one potential (PRNP) Zn2+ transporter in human postmortem brain tissue from Braak-staged individuals with AD and controls using quantitative real-time PCR. Four cortical regions (middle temporal gyrus, superior occipital gyrus, superior parietal gyrus, and superior frontal gyrus) and cerebellum were examined. PRNP mRNA levels were decreased by ∼30% in all four cortical regions examined in AD patients, but unchanged in the cerebellum. In contrast, some increases in mRNA levels of the other more established Zn2+ transporters (LIV1, ZIP1, ZnT1, ZnT6) were found in AD cortex. The ratios of the mRNA levels of LIV1, ZIP1, ZnT1, ZnT4, and ZnT6/mRNA level of neuron specific enolase increased significantly as the disease progressed and Braak stage increased. Significant correlations were also identified between mRNA levels of several of the Zn2+ transporters investigated. These expression changes could either reflect or cause the altered cortical Zn2+ distribution in AD, potentially increasing the likelihood of interactions between Zn2+ and Aβ or tau protein.
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, N. Ireland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Beyer
authors.forename: David T R
authors.initials: DT
authors.lastname: Coulson
authors.forename: Shirley
authors.initials: S
authors.lastname: Heggarty
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Jan
authors.initials: J
authors.lastname: Hellemans
authors.forename: G Brent
authors.initials: GB
authors.lastname: Irvine
authors.forename: Janet A
authors.initials: JA
authors.lastname: Johnston
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C498299:SLC30A1 protein, human; C491597:SLC30A4 protein, human; C504822:SLC30A6 protein, human; C403517:SLC39A1 protein, human; C418627:SLC39A6 protein, human; C017800:zinc-binding protein; D010751:Phosphopyruvate Hydratase