HDL Cholesterol and Alzheimer’s Neuropathology

Abstract & Commentary

Source: Launer LJ, et al. Cholesterol and neuropathologic markers of AD: A population based autopsy study. Neurology. 2001;57:1447-1452.

There has been increasing interest in a possible link between Alzheimer’s disease (AD) and elevated cholesterol following the reports that cholesterol-lowering medications such as the statins may reduce risk of dementia. Now, a new study has provided indirect evidence that components of HDL cholesterol may play a role in the development of the neuritic plaques and neurofibrillary tangles associated with AD.

Investigators at the NIH used information previously collected about circulating cholesterol levels and autopsy results from 218 Japanese-American men to carry out this study. They examined the correlation between plasma cholesterol levels at various stages of life and the appearance of plaques and neurofibrillary tangles in the brain after death. The study participants had been originally examined as part of the Honolulu Heart Program between 1965 and 1971. They were later re-examined between 1991 and 2001 as part of the Honolulu-Asia Aging Study. The investigators controled for a variety of possible confounding factors in their analysis, such as age at death, APOE genotype, midlife systolic blood pressure, as well as comorbid conditions such as stroke.

The subset of patients from the Honolulu-Asia Aging Study that underwent autopsy were found to be slightly older than the rest of the study population and had a greater representation of subjects affected by dementia. Of the 218 patients who underwent autopsies, 36 were found to have AD, 32 had vascular dementia, and 10 suffered from other dementias. A strong association was found between high late-life HDL cholesterol levels and increased numbers of neuritic plaques and tangles in the brain. Conversely, low levels of total cholesterol in midlife were associated with a lower number of neuritic plaques and neurofibrillary tangles. There was no such correlation found for diffuse and other non-neuritic plaques. It should be noted that there was no observed association between late life HDL cholesterol levels as a function of dementia diagnosis, such that similar findings were made in the pathologically confirmed cases of AD and vascular dementia.


This study found a dose response relationship between the number of neuritic plaques and tangles in autopsy cases of dementia and late life HDL cholesterol levels. The observed association was based upon a trend in the number of plaques and tangles in comparing patients with the lowest cholesterol levels to those with progressively higher HDL values. It is notable that this trend was observed based on the study of both demented and normal subjects. Therefore, this study provides no additional evidence that elevated serum cholesterol levels affect the risk of dementia. Nevertheless, the possibility that subtypes of cholesterol play a role in the development of selected elements of Alzheimer’s pathology is both biologically feasible and worthy of further study. —Norman R. Relkin

Dr. Relkin, Associate Professor of Clinical Neurology and Neuroscience, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.