期刊
MOLECULAR BIOLOGY REPORTS
卷 41, 期 10, 页码 6365-6376出版社
SPRINGER
DOI: 10.1007/s11033-014-3516-8
关键词
Alzheimer's disease; Autopsy brain tissue; RNA integrity; Apolipoprotein E; Alternative splicing; RT-qPCR
资金
- Neuroscience Research Australia
- University of New South Wales
- National Health and Medical Research Council (NHMRC)
- Australian Brain Bank Network
- University of Sydney
- NHMRC [605210]
- Schizophrenia Research Institute
- National Institutes of Alcoholism and Alcohol Abuse (NIAAA) [R24 AA012725]
The prevalence of Alzheimer's disease (AD) is increasing rapidly worldwide due to an ageing population and a lack of disease modifying therapeutics. In monogenic forms of AD mutations lead to the accumulation of neurotoxic peptides called beta-amyloid. Beta-amyloid accumulation is also postulated to precipitate sporadic AD although the pathogenesis of this common form remains largely unknown. The two leading risk factors for sporadic AD are ageing and the possession of the APOE epsilon 4 allele. Changes in APOE expression that are independent of the epsilon genotype have also been described in the AD brain including a recent RNA-Seq analysis that showed upregulation of a rare alternative splice isoform (APOE-005). To replicate these RNA-Seq findings we used quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) to compare APOE-005 and total APOE expression in the superior temporal gyrus of 14 AD cases and 16 neurologically normal controls. In AD, this area shows prominent beta-amyloid deposition but few neurofibrillary tangles and only moderate neuronal loss. As poorer RNA quality among the AD cases was a likely confounder in this study, the analysis was repeated in a RIN-matched sub-cohort of 17 individuals. Contrary to the original RNA-Seq study, we found no difference in total APOE, APOE-005 or the common isoform, APOE-001, between AD cases and controls. Our findings are consistent with ApoE acting largely at the protein level to increase the risk for sporadic AD.
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