Association of Alzheimer disease pathology with abnormal lipid metabolism
The Hisayama Study
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Abstract
Objective: The relationship between lipid profiles and Alzheimer disease (AD) pathology at the population level is unclear. We searched for evidence of AD-related pathologic risk of abnormal lipid metabolism.
Methods: This study included brain specimens from a series of 147 autopsies performed between 1998 and 2003 of residents in Hisayama town, Japan (76 men and 71 women), who underwent clinical examinations in 1988. Lipid profiles, such as total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDLC), were measured in 1988. Low-density lipoprotein cholesterol (LDLC) was calculated using the Friedewald formula. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines (CERAD) and neurofibrillary tangles (NFTs) were assessed according to Braak stage. Associations between each lipid profile and AD pathology were examined by analysis of covariance and logistic regression analyses.
Results: Adjusted means of TC, LDLC, TC/HDLC, LDLC/HDLC, and non-HDLC (defined as TC–HDLC) were significantly higher in subjects with NPs, even in sparse to moderate stages (CERAD = 1 or 2), compared to subjects without NPs in multivariate models including APOE ε4 carrier and other confounding factors. The subjects in the highest quartiles of these lipid profiles had significantly higher risks of NPs compared to subjects in the lower respective quartiles, which may suggest a threshold effect. Conversely, there was no relationship between any lipid profile and NFTs.
Conclusion: The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology.
Footnotes
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Study funding: Supported by a Grant-in-Aid for Scientific Research (B) (No. 22300116) and (C) (No. 21500337) from Japan Society for the Promotion of Science (JSPS) and by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan (Comprehensive Research on Aging and Health: H20-Chouju-004). The funders of the present study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
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Supplemental data at www.neurology.org
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- AD=
- Alzheimer disease;
- CERAD=
- Consortium to Establish a Registry for Alzheimer's Disease;
- CI=
- confidence interval;
- HDLC=
- high-density lipoprotein cholesterol;
- LDLC=
- low-density lipoprotein cholesterol;
- NFT=
- neurofibrillary tangle;
- NP=
- neuritic plaque;
- OR=
- odds ratio;
- TC=
- total cholesterol;
- TG=
- triglycerides
- Received February 16, 2011.
- Accepted May 23, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence
- Alzheimer disease pathology is associated with higher serum cholesterol and LDL
- Gerson T. Lesser, Adjunct Clinical Professor (Geriatrics & Medicine), Mount Sinai School of Medicinegtl1@nyu.edu
Submitted January 30, 2012 - Reply from authors
- Kensuke Sasaki, Assistant Professor, Kyushu University, Japanksasaki@np.med.kyushu-u.ac.jp
- Toru Iwaki
Submitted October 07, 2011 - Cholesterol, statin therapy and neuritic plaque in Alzheimer's disease
- Luca Mascitelli, Medical Officer, Comando Brigata alpina Julia, Udine, Italylumasci@libero.it
- Stephanie Seneff, Mark R. Goldstein
Submitted September 29, 2011
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