Pathologically Confirmed Alzheimer's Disease in APOE ϵ2 Homozygotes is Rare but Does Occur
Background: Homozygous APOE ϵ4 status is a well-known risk factor in the development of Alzheimer's disease (AD). However, other genotypes of APOE have not yet been found to have equal clinical significance. There is a paucity of reports regarding clinically or pathologically described AD in APOE ϵ2 homozygotes compared to the other alleles. Objective: To notify clinicians that patients with homozygous APOE ϵ2 are also at risk of developing AD based on results from the largest prospectively gathered registry of brain samples to date. Methods: We queried the National Alzheimer's Coordinating Center (NACC) database for autopsy-confirmed AD cases. Of the Uniform Data Set (UDS) participants who are deceased, 5,779 were diagnosed with dementia at their last UDS visit prior to death, and autopsy data is available for 3,518. Results: Of the brains in the NACC database with pathologically confirmed dementia, seven were found to be homozygous for APOE ϵ2, which represents only 0.2% of the autopsy-confirmed sample. Furthermore, pathology-confirmed AD represents 29% (2/7) of the APOE ϵ2/ϵ2 patients diagnosed with dementia. Conclusions: Although rare, autopsy-confirmed AD can be present in APOE ϵ2/ϵ2 carriers.
Journal of Alzheimer's Disease
Digital Object Identifier (DOI)
Stipho, Faissal; Jackson, Robert; and Sabbagh, Marwan N., "Pathologically Confirmed Alzheimer's Disease in APOE ϵ2 Homozygotes is Rare but Does Occur" (2018). Neurology. 979.