Olfactory Dysfunction in ApoE ɛ4/4 Homozygotes with Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory impairment and the presence of amyloid plaques and neurofibrillary tangles. The associated neuropathology originates in brain areas responsible for olfaction, which makes olfactory tasks potentially useful for assessing AD. The strongest genetic risk factor for AD is the apolipoprotein E (ApoE) ɛ4 allele that has been associated with increased cognitive and olfactory deficits. While individuals carrying one ɛ4 allele of the ApoE gene are at increased risk for AD relative to non-carriers, those with two copies of the ɛ4 allele demonstrate an even higher risk for developing AD. Furthermore, homozygous ApoE ɛ4/4 individuals diagnosed with AD are known to have heightened amyloid burden and a more rapid rate of cognitive decline relative to heterozygous ɛ3/4 ApoE carriers. All of these factors suggest there are differences in severity and progression of AD as a function of possessing one versus two ɛ4 alleles. The current study investigated olfactory functioning in homozygous ɛ4/4 older adults diagnosed with probable AD. Compared to demographically matched ɛ3/3 and ɛ3/4 individuals, ɛ4/4 individuals showed deficits in odor identification and remote odor memory as measured by odor familiarity ratings. The current findings suggest that these particular domains of olfactory functioning may be more impaired in AD ɛ4/4 homozygotes compared to ɛ3/4 heterozygotes and ɛ3/3 homozygotes. These deficits give insight into how the presence of two ɛ4 alleles may differentially affect the progression of AD and suggest the usefulness of odor tasks in detecting those at risk for AD.