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

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

Abstract

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. Methods: We investigated the association between APOE genotypes and neuropathological and cognitive data in this cohort (n=310). Results:APOEε4 was associated with an increased risk of diffuse plaques, neuritic plaques, tangles and cerebral amyloid angiopathy. APOEε4 was not associated with infarcts, lacunes, haemorrhages or small vessel disease. APOEε2 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. 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 APOEε4 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 mechanisms. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Citation

Nicoll, J. A., Savva, G. M., Stewart, J., Matthews, F. E., Brayne, C., & Ince, P. (2011). Association between APOE genotype, neuropathology and dementia in the older population of England and Wales. Neuropathology and Applied Neurobiology, 37(3), 285-294. https://doi.org/10.1111/j.1365-2990.2010.01130.x

• Journal Article Type: Article
• Publication Date: Apr 1, 2011
• Deposit Date: Dec 8, 2023
• Journal: Neuropathology and Applied Neurobiology
• Print ISSN: 0305-1846
• Electronic ISSN: 1365-2990
• Publisher: British Neuropathological Society
• Volume: 37
• Issue: 3
• Pages: 285-294
• DOI: https://doi.org/10.1111/j.1365-2990.2010.01130.x
• Public URL: https://hull-repository.worktribe.com/output/4454906