APOE, vascular pathology, and the AD brain

Area of Science:

• Neuropathology
• Genetics
• Neurodegenerative Diseases

Background:

• Alzheimer disease (AD) is characterized by cerebrovascular lesions, neuritic senile plaques (SP), and neurofibrillary tangles (NFT).
• The apolipoprotein E (APOE) genotype, particularly the epsilon4 allele, is a known risk factor for AD.
• The specific neuropathologic correlates of APOE-epsilon4 in AD remain incompletely understood.

Purpose of the Study:

• To investigate the association between APOE genotype and neuropathologic findings in autopsy-proven Alzheimer disease.
• To examine the relationship between APOE-epsilon4 and cerebrovascular lesions, including arteriolosclerosis and microinfarcts.
• To assess the association of APOE-epsilon4 with neuritic senile plaque (SP) and neurofibrillary tangle (NFT) burden.

Main Methods:

• Neuropathologic examination of brains from 99 individuals meeting NIA-Reagan criteria for AD.
• Comparison of cerebrovascular pathology (arteriolosclerosis, white matter lesions, microinfarcts, amyloid angiopathy) and AD pathology (SP, NFT) between APOE-epsilon4 carriers and non-carriers.
• Statistical analysis adjusting for age, sex, brain weight, and Braak stage.

Main Results:

• APOE-epsilon4 was associated with increased small vessel arteriolosclerosis and microinfarcts in deep nuclei.
• A trend towards association was observed between APOE-epsilon4 and amyloid angiopathy.
• APOE-epsilon4 was significantly associated with a higher burden of neuritic SP but not NFT.

Conclusions:

• APOE-epsilon4 is implicated in specific microvascular pathologies, including arteriolosclerosis and deep nuclear microinfarcts, in AD.
• The findings support a potential role for APOE-epsilon4 in amyloid angiopathy and neuritic plaque formation in AD.
• These results highlight the contribution of APOE genotype to the vascular component of Alzheimer disease pathology.