title: Aging-related changes in blood-brain barrier integrity and the effect of dietary fat.
abstract: BACKGROUND
  Disturbances in blood-brain barrier (BBB) integrity contribute to the onset and progression of neurodegenerative diseases including Alzheimer's disease (AD) and vascular dementia (VaD). Aging is positively associated with AD and VaD risk, but this may reflect comorbidities or the effects of other chronic modulators of vascular function such as diet.
  
  
  OBJECTIVE
  To explore putative synergistic effects of aging with diet, in this study genetically unmanipulated mice were maintained on diets enriched in saturated fatty acids (SFA) or cholesterol and compared to mice provided with low-fat (LF) feed formula.
  
  
  METHODS
  The functional integrity of the BBB was assessed following 3, 6 and 12 months of dietary intervention commenced at 6 weeks of age, by determining the brain parenchymal extravasation of immunoglobulin G (IgG).
  
  
  RESULTS
  Mice maintained on the SFA- or cholesterol-enriched diet showed significant parenchymal IgG abundance following 3 months of feeding, concomitant with diminished expression of the tight junction protein occludin. LF control mice had essentially no evidence of BBB disturbances. Six months of SFA feeding exacerbated the difference in IgG abundance compared to the LF mice. At 12 months of feeding, the control LF mice also had significant parenchymal IgG that was comparable to mice fed the SFA- or cholesterol-enriched diet for 3 months. However, there may have been an adaptation to the fat-enriched diets because SFA and cholesterol did not exacerbate IgG parenchymal accumulation beyond 6 months of feeding.
  
  
  CONCLUSIONS
  Collectively, the study suggests that diets enriched in SFA or cholesterol accelerate the onset of BBB dysfunction that otherwise occurs with aging.
authors.affiliation: Curtin Health Innovation Research Institute, Faculty of Health Science, School of Public Health, Curtin University, Perth, W.A., Australia.
authors.forename: R
authors.initials: R
authors.lastname: Takechi
authors.forename: M M
authors.initials: MM
authors.lastname: Pallebage-Gamarallage
authors.forename: V
authors.initials: V
authors.lastname: Lam
authors.forename: C
authors.initials: C
authors.lastname: Giles
authors.forename: J C
authors.initials: JC
authors.lastname: Mamo
mesh_terms: D000375:Aging; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004041:Dietary Fats