Pathologically Confirmed Alzheimer's Disease in APOE ɛ2 Homozygotes is Rare but Does Occur.

BACKGROUND

Homozygous APOEɛ4 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 APOEɛ2 homozygotes compared to the other alleles.

OBJECTIVE

To notify clinicians that patients with homozygous APOEɛ2 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 APOEɛ2, which represents only 0.2% of the autopsy-confirmed sample. Furthermore, pathology-confirmed AD represents 29% (2/7) of the APOEɛ2/ɛ2 patients diagnosed with dementia.

CONCLUSIONS

Although rare, autopsy-confirmed AD can be present in APOEɛ2/ɛ2 carriers.