title: Effect of apolipoprotein E genotype and diet on apolipoprotein E lipidation and amyloid peptides: randomized clinical trial.
abstract: OBJECTIVE
  Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the β-amyloid (Aβ) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing Aβ, and LD Aβ peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid.
  
  
  OBJECTIVE
  To characterize the lipidation states of Aβ peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ε4 allele carrier status and after a dietary intervention.
  
  
  METHODS
  Randomized clinical trial.
  
  
  METHODS
  Veterans Affairs Medical Center clinical research unit.
  
  
  METHODS
  Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years).
  
  
  METHODS
  Randomization to a diet high in saturated fat content and with a high glycemic index (High diet; 45% of energy from fat [>25% saturated fat], 35%-40% from carbohydrates with a mean glycemic index >70, and 15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein).
  
  
  METHODS
  Lipid-depleted Aβ42 and Aβ40 and apolipoprotein E in cerebrospinal fluid.
  
  
  RESULTS
  Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD Aβ42, P = .05; LD Aβ40, P = .01). These findings were magnified in adults with mild cognitive impairment and the ε4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P < .001). The Low diet tended to decrease LD Aβ levels, whereas the High diet increased these fractions (LD Aβ42, P = .01; LD Aβ40, P = .15). Changes in LD Aβ levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD Aβ42 and insulin, r = -0.68 [P = .01]; LD Aβ40 and insulin, r = -0.78 [P = .002]).
  
  
  CONCLUSIONS
  The lipidation states of apolipoproteins and Aβ peptides in the brain differ depending on APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet. These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy diets impart risk for developing AD.
authors.affiliation: Geriatric Research, Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Hanson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bayer-Carter
authors.forename: Pattie S
authors.initials: PS
authors.lastname: Green
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Charles W
authors.initials: CW
authors.lastname: Wilkinson
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.forename: G Stennis
authors.initials: GS
authors.lastname: Watson
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bonner
authors.forename: Maureen
authors.initials: M
authors.lastname: Callaghan
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Elaine
authors.initials: E
authors.lastname: Tsai
authors.forename: Nadia
authors.initials: N
authors.lastname: Postupna
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Johanna
authors.initials: J
authors.lastname: Lampe
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000178:diet therapy / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000009:adverse effects / Q000134:cerebrospinal fluid* / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000178:diet therapy / Q000235:genetics; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014481:United States
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D004041:Dietary Fats; D010446:Peptide Fragments; C538897:amyloid beta-protein (40-42)