October 23, 2001
View Full PaperCholesterol and neuropathologic markers of AD
Key Result
Increasing late-life HDL cholesterol levels were strongly associated with an increased number of neocortical neuritic plaques (count ratio 2.30; 95% CI 1.05-5.06) and neurofibrillary tangles.
Study Design
Type
Observational (n=218)
Blinding
Blinded to clinical information
Structured PICO
Are plasma cholesterol levels associated with neuropathologic markers of Alzheimer's disease in older Japanese American men?
P
Population
218 Japanese American men from the Honolulu-Asia Aging Study, average age at death 84.6 years
I
Intervention
Plasma cholesterol levels (total, HDL, and LDL) measured in late life and midlife
C
Comparator
Lowest quintile of cholesterol levels
O
Outcome
Counts of neuritic plaques (NP) and neurofibrillary tangles (NFT) in neocortex and hippocampussurrogate
Higher HDL cholesterol levels in late life are associated with increased neuropathologic markers of Alzheimer's disease, suggesting HDL constituents may play a role in AD pathology.
Main Result
Effect estimate: count ratio 2.30 (95% CI 1.05 to 5.06)
Abstract
OBJECTIVE: To examine the association of plasma cholesterol (total and high-density HDL and low-density lipoprotein) levels with neuritic plaques (NP) and neurofibrillary tangles (NFT) in a population-based autopsy series of 218 Japanese American men followed as a part of the Honolulu-Asia Aging Study. METHODS: Cholesterol levels were measured in late life (average age at death 84.6 years) in all subjects (n = 218) and in midlife (20 years before late life) in a subsample (n = 89); for the analyses, levels were categorized into quintiles, with the lowest quintile serving as the reference. Tissue from four areas of neocortex and two areas of hippocampus was prepared with Bielschowsky silver-stained sections and evaluated by one of three neuropathologists who were blinded to clinical information. Diffuse and neuritic plaques and NFT were counted in field areas standardized to 1 mm(2). Fields were selected from areas with the highest numbers of lesions, and the field with the highest count was taken to represent the brain area. RESULTS: After adjusting for age at death, education, APOE allele, dementia, neuropathologic infarction, and blood pressure, a strong linear association was found for increasing late-life HDL cholesterol (HDL-C) levels and an increasing number of neocortical NP (5th versus 1st quintile: count ratio 95% CI 2.30 1.05 to 5.06) and hippocampal (2.63 1.25 to 5.50) and neocortical (4.20 1.73 to 10.16) NFT. Trends were similar for the midlife HDL-C levels. CONCLUSIONS: The constituents of HDL-C may play a role in the formation of AD pathology, and these processes are reflected in peripheral measures.