Skip to main content
Article thumbnail
Location of Repository

Association between APOE genotype, neuropathology and dementia in the older population of England and Wales

By J.A.R. Nicoll, G.M. Savva, J. Stewart, F.E. Matthews, C. Brayne and P. Ince


Aims: apolipoprotein E (APOE) genotype is the major genetic risk factor for sporadic Alzheimer's disease (AD) but it is unclear how this is mediated. Most studies of APOE genotype have used case–control design to compare groups differing by two variables: i.e. dementia and AD pathology, so it is unclear to which of these variables APOE genotype is more strongly related. The prospective Medical Research Council Cognitive Function and Ageing Study neuropathology cohort is population-based sample in which donations are unbiased by dementia status. <br/><br/>Methods: we investigated the association between APOE genotypes and neuropathological and cognitive data in this cohort (n = 310). <br/><br/>Results: APOE?4 was associated with an increased risk of diffuse plaques, neuritic plaques, tangles and cerebral amyloid angiopathy. APOE?4 was not associated with infarcts, lacunes, haemorrhages or small vessel disease. APOE?2 appeared to have a protective effect on AD pathology and also on the risk of cortical atrophy. APOE genotype had a non-significant effect on the presence of dementia after adjusting for AD pathology. <br/><br/>Conclusions: APOE genotype is associated with each of the key features of AD pathology but not with cerebrovascular disease other than cerebral amyloid angiopathy. The excess risk of dementia in those with an APOE?4 allele is explained by the pathological features of AD. However, it remains unclear to what extent cognitive dysfunction is caused by these specific pathological features or more directly by closely related APOE-associated mechanism

Topics: RC0321
Year: 2011
OAI identifier:
Provided by: e-Prints Soton
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • (external link)
  • Suggested articles

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.