Research project Alzheimer´s disease is a fat problem

In the proposed studies we will investigate a potential AD-causal relationship between elevated peripheral triglycerides and pathological processes leading to neurodegeneration of the brain. Triglycerides, opposite to cholesterol, are known to cross the blood-brain-barrier where they have been shown to promote pathological conditions when present in higher concentrations. We will use fluid samples from three different clinical cohorts including sporadic and familial AD patients to establish a relationship between the APOE4 AD risk-allele, the lipases that regulate triglyceride levels in the periphery, and triglyceride levels per se in plasma, disease status and progression. We will further use primary human hepatocytes, cultured iPSC-derived human neurons and a mouse model with humanized livers to study a direct relationship between APOE genotype, peripheral lipases, triglyceride levels and pathological processes leading to synaptic deficits and neurodegeneration in the brain. Timely and appropriate management of peripheral triglyceride levels we believe may be a viable target for disease modification and prevention of AD.