Zinc Transporter mRNA Levels in Alzheimer's Disease Postmortem Brain

Article type: Research Article

Authors: Beyer, Nancy^a | Coulson, David T.R.^a | Heggarty, Shirley^b | Ravid, Rivka^c | Hellemans, Jan^d | Irvine, G. Brent^a | Johnston, Janet A.^{a; *}

Affiliations: [a] Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, N. Ireland | [b] Genomics Core Facility, Regional Genetics Centre, Belfast City Hospital, Belfast, N. Ireland | [c] Netherlands Institute for Neurosciences, Amsterdam, The Netherlands | [d] Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium

Correspondence: [*] Correspondence to: Dr. Janet A. Johnston, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Institute of pathology, Grosvenor Road, Belfast BT12 6BJ, N. Ireland. Tel.: +44 2890635011; Fax: +44 2890235900; E-mail: [email protected].

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.

Keywords: LIV1 protein, neurodegenerative diseases, prion protein, reverse transcriptase polymerase chain reaction, zinc, ZIP1 protein, ZnT1 protein, ZnT4 protein, ZnT6 protein

DOI: 10.3233/JAD-2012-112105

Journal: Journal of Alzheimer's Disease, vol. 29, no. 4, pp. 863-873, 2012