title: Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study.
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.
  
  
  CONCLUSIONS
  The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology.
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: J
authors.initials: J
authors.lastname: Hata
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: K
authors.initials: K
authors.lastname: Fujimi
authors.forename: T
authors.initials: T
authors.lastname: Ninomiya
authors.forename: S O
authors.initials: SO
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Kanba
authors.forename: Y
authors.initials: Y
authors.lastname: Kiyohara
authors.forename: T
authors.initials: T
authors.lastname: Iwaki
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D050171:Dyslipidemias / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D012042:Registries