Because of the elongation average life span of the population neurodegenerative disorders like Alzheimer¿s disease (AD), characterized in particular by the pathological accumulation of amyloid peptide beta (Aß),
Represent a significant problem for public health. Recent evidence has shown the important role of the Blood-Brain Barrier (BBB) in AD which alterations are responsible for the reduction of glucose transporters in the brain and increased deposition of the amyloid peptide.
AD develops asymptomatically to become clinically evident only in the later stage. This delay implies the possibility of promoting early interventions, like dietary intervention such us Ketogenic diet to promote the delay or prevent the AD onset. Through the production of Ketone bodies (KBs), this diet seems to be able to ameliorate cognitive function in human subjects and animal models. KBs in fact, represent the alternative energy source for the brain, and unlike glucose, their transport mechanism across the BBB is not affected in AD. The action of KBs is not well elucidated, especially at the BBB level. Our preliminary results showed an effect of KD on brain microvessels in vivo; therefore our project aims at investigating KD and KBs activity in in vitro cellular models. Our system taking advantage of an in vitro human BBB model should confirm the in vivo results and demonstrate the importance of BBB in AD
Previous studies have investigated processes underlying the production and accumulation of the amyloid peptide. Our attention will instead focus on the BBB, studying for the first time the mechanisms of transport of amyloid peptide as well as KBs, related to ketogenic diet.
The use of an in vitro model will allow us to characterize the effects of the KBs on the different cellular types that constitute, in vivo, the brain microvessels by transcriptional and epigenetics approaches.
We recreate the microenvironment induced by ketogenic diet by adding KBs to the cultures, recreating for the first time an in vitro model of ketosis state, to study the exchanges of A-ß peptides and KBs from the brain to the blood and viceversa at the BBB level.