Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease?
The premature presence of senile plaques (SP) in coronary artery disease (CAD), and neurofibrillary tangles (NFT) as well as SP in hypertension (HyperT), suggest a neuropathologic link between CAD, HyperT, and AD. Previous MI, CAD and HyperT often occur in and may increase the risk of AD. Expression of Apo-E4 likely increases risk of CAD by elevating blood cholesterol and the risk of AD via proposed interactions with beta-amyloid and/or free radicals (FRs). Any Apo-E4 effect is vague, but FRs probably mediate vascular damage in HyperT. Increasing FR content in the blood is related to increasing CAD severity, while the severity of elevated FR level correlates with how deep into a blood vessel there is activation of the FR scavenger enzyme, superoxide dismutase (SOD). The ApoE genotype and SP/NFT areal densities were determined in a large population of non-demented CAD, HyperT and non-heart disease (non-HD) control subjects, and compared to findings in a similar number of AD patients. ApoE immunoreactivity was determined in many individuals. Cholesterol content in cortex was determined by HPLC in a small, loosely age-matched group of Apo-E4 genotype-matched AD, CAD and non-HD subjects. SOD immunoreactivity was also assessed in a number of subjects. The Apo-E4 genotype frequency was increased in CAD, HyperT and AD compared to non-HD controls. Dose of Apo-E4 correlated with SP densities, but not NFT, and only in the non-demented groups. Essentially all SP in CAD, HyperT and non-HD subjects were ApoE-immunoreactive. Cortical cholesterol was increased in CAD and AD compared to controls. SOD immunoreactivity was similar in HyperT and AD; SP were immunodecorated in both. AD, CAD and HyperT may be linked, while CAD and HyperT subjects may die of heart disease before showing cognitive change.
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Division of Medical Examiner's Services, Kentucky Justice Cabinet, Frankfort, USA.
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D013482:Superoxide Dismutase / Q000032:analysis
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002784:Cholesterol; D013482:Superoxide Dismutase