Affiliations: [a] Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland | [b] Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium | [c] Brain Bank Consultants, Amstelveen, The Netherlands | [d] Netherlands Institute for Neurosciences, Amsterdam, The Netherlands
Correspondence:
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Correspondence to: Dr. Janet Johnston, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Institute of Clinical Sciences B, Room 02014, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland. Tel.: +44 2890635011; Fax: +44 2890235900; E-mail: [email protected].
Note: [] Handling Associate Editor: Craig Atwood
Abstract: β-site AβPP cleaving enzyme 1 (BACE1) catalyses the rate-limiting step for production of amyloid-β (Aβ) peptides, involved in the pathological cascade underlying Alzheimer's disease (AD). Elevated BACE1 protein levels and activity have been reported in AD postmortem brains. Our study explored whether this was due to elevated BACE1 mRNA expression. RNA was prepared from five brain regions in three study groups: controls, individuals with AD, and another neurodegenerative disease group affected by either Parkinson's disease (PD) or dementia with Lewy bodies (DLB). BACE1 mRNA levels were measured using quantitative realtime PCR (qPCR) and analyzed by qbasePLUS using validated stably-expressed reference genes. Expression of glial and neuronal markers (glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), respectively) were also analyzed to quantify the changing activities of these cell populations in the tissue. BACE1 mRNA levels were significantly elevated in medial temporal and superior parietal gyri, compared to the PD/DLB and/or control groups. Superior frontal gryus BACE1 mRNA levels were significantly increased in the PD/DLB group, compared to AD and control groups. For the AD group, BACE1 mRNA changes were analyzed in the context of the reduced NSE mRNA, and strongly increased GFAP mRNA levels apparent as AD progressed (indicated by Braak stage). This analysis suggested that increased BACE1 mRNA expression in remaining neuronal cells may contribute to the increased BACE1 protein levels and activity found in brain regions affected by AD.
