Presenter of 1 Presentation
IMPACT OF APOE ON AD/ADRD NEUROPATHOLOGIC LESIONS.
Abstract
Aims
Alzheimer disease (AD) is primarily driven by genetics, though much is still unknown. The strongest genetic risk factor for AD is APOE, shown mostly in clinically diagnosed AD. To get closer to the underlying genetics, we investigate the neuropathological changes in the AD brain including neurofibrillary tangles (NFT), neuritic plaques (NP), and diffuse plaques (DP). AD lesions often co-occur with AD-related dementia (ADRD) lesions including Lewy Bodies (LB), cerebral amyloid angiopathy (CAA), arteriolosclerosis (ARTE), hippocampal sclerosis (HS), vascular brain injury (VBI), and TAR DNA-binding protein 43 (TDP-43) inclusions. Previously, we showed that higher lesion comorbidity is associated with more severe cognitive impairment. Herein, we report on the influence of the APOE genotype on AD/ADRD lesions.
Methods
Using the NACC database, we identified 3,787 individuals with neuropathology data and APOE genotype. Lesions were ranked ordinally based on increasing severity. APOE status was categorized by genotype. Ordinal logistic regression models assessed associations between APOE genotypes and lesions, adjusting for age at death and sex.
Results
Regression models show that APOE e4 is strongly associated with severity of NFT, NP, DP, and CAA (p<1.0E-10), and is nominally associated with TDP-43, LB, HS, and VBI (p<0.05), but not with the severity of ARTE (p>0.05).
Conclusions
APOE e2 behaves protectively against lesion severity while APOE e4 has a multiplicative risk effect on the 3 AD lesions, CAA, and TDP-43. The other ADRD lesions are not strongly associated with APOE genotypes and are likely influenced by other genetic factors.