Abstract
BackgroundLate onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia. Multiple genetic loci, including 10q, have been implicated in LOAD but to date, with the exception of APOE, the underlying genes have not been identified. HECTD2 maps to 10q and has been implicated in susceptibility to human prion diseases which are also neurodegenerative conditions associated with accumulation of misfolded host proteins. In this study we test whether the HECTD2 susceptibility allele seen in prion disease is also implicated in LOAD.MethodsDNA from 320 individuals with Alzheimer's disease and 601 controls were genotyped for a HECTD2 intronic tagging SNP, rs12249854 (A/T). Groups were further analysed following stratification by APOE genotype.ResultsThe rs12249854 minor allele (A) frequency was higher (5.8%) in the Alzheimer's disease group as compared to the controls (3.9%), however, this was not statistically significant (P = 0.0668). No significant difference was seen in minor allele frequency in the presence or absence of the APOE ε4 allele.ConclusionThe common haplotypes of HECTD2, tagged by rs12249854, are not associated with susceptibility to LOAD.
Highlights
Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia
The main genetic risk factor for late onset Alzheimer's disease (LOAD) is the apolipoprotein E gene (APOE) where the ε4 allele is over-represented in affected individuals (50%) compared to controls [8]
We have previously shown that strong linkage disequilibrium (LD) extends across the whole of the HECTD2 gene and interrogation of HapMap data suggests that this block of LD does not extend into neighbouring genes [20]
Summary
Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia. Multiple genetic loci, including 10q, have been implicated in LOAD but to date, with the exception of APOE, the underlying genes have not been identified. HECTD2 maps to 10q and has been implicated in susceptibility to human prion diseases which are neurodegenerative conditions associated with accumulation of misfolded host proteins. The main genetic risk factor for late onset Alzheimer's disease (LOAD) is the apolipoprotein E gene (APOE) where the ε4 allele is over-represented in affected individuals (50%) compared to controls [8]. The partial penetrance for ε4 suggests that other genes are likely to be important in the development of LOAD [9]
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