Differential effects of dietary fatty acids on the cerebral distribution of plasma-derived apo B lipoproteins with amyloid-beta.
Some dietary fats are a risk factor for Alzheimer's disease (AD) but the mechanisms for this association are presently unknown. In the present study we showed in wild-type mice that chronic ingestion of SFA results in blood-brain barrier (BBB) dysfunction and significant delivery into the brain of plasma proteins, including apo B lipoproteins that are endogenously enriched in amyloid-beta (Abeta). Conversely, the plasma concentration of S100B was used as a marker of brain-to-blood leakage and was found to be increased two-fold because of SFA feeding. Consistent with a deterioration in BBB integrity in SFA-fed mice was a diminished cerebrovascular expression of occludin, an endothelial tight junction protein. In contrast to SFA-fed mice, chronic ingestion of MUFA or PUFA had no detrimental effect on BBB integrity. Utilising highly sensitive three-dimensional immunomicroscopy, we also showed that the cerebral distribution and co-localisation of Abeta with apo B lipoproteins in SFA-fed mice are similar to those found in amyloid precursor protein/presenilin-1 (APP/PS1) amyloid transgenic mice, an established murine model of AD. Moreover, there was a strong positive association of plasma-derived apo B lipoproteins with cerebral Abeta deposits. Collectively, the findings of the present study provide a plausible explanation of how dietary fats may influence AD risk. Ingestion of SFA could enhance peripheral delivery to the brain of circulating lipoprotein-Abeta and exacerbate the amyloidogenic cascade.
Takechi
Ryusuke
R
Faculty of Health Science, School of Public Health, Curtin University of Technology, Bentley, WA, Australia.
Galloway
Susan
S
Pallebage-Gamarallage
Menuka M S
MM
Wellington
Cheryl L
CL
Johnsen
Russell D
RD
Dhaliwal
Satvinder S
SS
Mamo
John C L
JC
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D053299:Apolipoprotein B-100 / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy / Q000379:methods; D062793:Occludin; D053764:Presenilin-1; D012307:Risk Factors; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D053299:Apolipoprotein B-100; D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D053764:Presenilin-1