title: Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology.
abstract: BACKGROUND
  Epidemiologic and experimental data suggest that cholesterol may play a role in the pathogenesis of AD. Modulation of cholesterolemia in transgenic animal models of AD strongly alters amyloid pathology.
  
  
  OBJECTIVE
  To determine whether a relationship exists between amyloid deposition and total cholesterolemia (TC) in the human brain.
  
  
  METHODS
  The authors reviewed autopsy cases of patients older than 40 years and correlated cholesterolemia and presence or absence of amyloid deposition (amyloid positive vs amyloid negative subjects) and cholesterolemia and amyloid load. Amyloid load in human brains was measured by immunohistochemistry and image analysis. To remove the effect of apoE isoforms on cholesterol levels, cases were genotyped and duplicate analyses were performed on apoE3/3 subjects.
  
  
  RESULTS
  Cholesterolemia correlates with presence of amyloid deposition in the youngest subjects (40 to 55 years) with early amyloid deposition (diffuse type of senile plaques) (p = 0.000 for all apoE isoforms; p = 0.009 for apoE3/3 subjects). In this group, increases in cholesterolemia from 181 to 200 almost tripled the odds for developing amyloid, independent of apoE isoform. A logistic regression model showed consistent results (McFadden rho2 = 0.445). The difference in mean TC between subjects with and without amyloid disappeared as the age of the sample increased (>55 years: p = 0.491), possibly reflecting the effect of cardiovascular deaths among other possibilities. TC and amyloid load were not linearly correlated, indicating that there are additional factors involved in amyloid accumulation.
  
  
  CONCLUSIONS
  Serum hypercholesterolemia may be an early risk factor for the development of AD amyloid pathology.
authors.affiliation: University of South Alabama, Mobile, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pappolla
authors.forename: T K
authors.initials: TK
authors.lastname: Bryant-Thomas
authors.forename: D
authors.initials: D
authors.lastname: Herbert
authors.forename: J
authors.initials: J
authors.lastname: Pacheco
authors.forename: M
authors.initials: M
authors.lastname: Fabra Garcia
authors.forename: M
authors.initials: M
authors.lastname: Manjon
authors.forename: X
authors.initials: X
authors.lastname: Girones
authors.forename: T L
authors.initials: TL
authors.lastname: Henry
authors.forename: E
authors.initials: E
authors.lastname: Matsubara
authors.forename: D
authors.initials: D
authors.lastname: Zambon
authors.forename: B
authors.initials: B
authors.lastname: Wolozin
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: F F
authors.initials: FF
authors.lastname: Cruz-Sanchez
authors.forename: L J
authors.initials: LJ
authors.lastname: Thal
authors.forename: S S
authors.initials: SS
authors.lastname: Petanceska
authors.forename: L M
authors.initials: LM
authors.lastname: Refolo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013702:Temporal Lobe / Q000737:chemistry / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D020033:Protein Isoforms