Affiliations: [a] Laboratory of Neuropsychiatry, The Neuroscience Center, Rigshospitalet-6102, and Department of Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark | [b] Netherlands Brain Bank, Meibergdreef 33, NL-1105 AZ Amsterdam, The Netherlands | [c] Institute of Pathology (Neuropathology), Vrije Universiteit Medisch Centrum, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands
Abstract: Apolipoprotein E (APOE) allele ε4 is a risk factor for Alzheimer's disease (AD) and has also been associated with impaired recovery from brain injury. Previous studies on APOE ε4 in dementing disorders other than AD have been rather conflicting, in particular concerning frontotemporal dementia (FTD) and vascular dementia (VD). In the present study we determined APOE genotype in an autopsy series of demented subjects and non-demented controls from the Netherlands Brain Bank. We attempted to create as clear-cut diagnostic groups as possible and paid close attention to AD-type histopathological changes in all cases. In comparison with the APOE ε4 allele frequency in controls (0.12; n=163 subjects), the APOE ε4 allele frequency was significantly increased in AD (0.42; n=320, p<0.0001), as well as in AD with Lewy bodies (0.43; n=41, p<0.0001) and in demented subjects with no other neuropathological findings than AD-histopathology insufficient for a diagnosis of AD (0.29; n=41, p<0.001). However, the APOE ε4 allele frequency was not significantly increased in FTD (0.18; n=49), VD (0.10; n=20) or in Lewy body disease without concomitant AD changes (0.13; n=12). As concerns dementing disorders, our results suggest that APOE ε4 is selectively associated with the presence of AD-type histopathology.
