Silvia Maioli Group
Over the years, genetic and epidemiological studies have reported gene or environmental factors that increase the risk for AD, suggesting that it is a disease of multifactorial origin. We aim to contribute to understand the effects of risk factors for AD: apolipoprotein E (apoE), diabetes, serum cholesterol and cholesterol metabolites in the brain and to define to which extent these factors are secondary actors or driving forces for cognitive decline.
Mechanisms behind risk factors for Alzheimer disease (AD)
Apolipoprotein E, hypercholesterolemia and AD
ApoE is the main cholesterol transporter and the presence of the E4 isoform is the major risk factor for AD. High cholesterol levels in blood is another risk factor. Our hypothesis is that ApoE4 acts in synergy with environmental factors (like hypercholesterolemia) to affect signalling pathways involved in neurodegeneration. We use several in vivo and in vitro models to explore this hypothesis.
Functions of oxysterols in brain
The metabolism of cholesterol results in the production of several oxysterols, of which the peripherally-produced 27OHC and the brain-produced 24S-OH have been suggested to play a role in AD pathogenesis. However very little is known about the biological role of these oxysterols, with the exception of its affinity for LXR receptors. We have discovered new functions of 24S-OH and 27OHC in brain, related with memory consolidation and vascular regulation. Our findings suggest that these molecules are much more than subproducts of the cellular metabolism, and can be regarded as signalling molecules of importance for normal brain function as well as for neurodegeneration.