BRFAA - Biomedical Research Foundation Academy Of Athens
Biomedical Research Foundation Academy Of AthensAcademy Of Athens

Research

My research focuses on the understanding of the molecular and cellular machanisms of Alzheimer’s disease, using primarily mouse genetics, as well as biochemical, molecular and cell biological approaches. My hypothesis is that the cholesterol transport system and inflammation play a major role in disease pathogenesis and progression. Our studies have shown that the cholesterol receptors, SR-BI and LDLR, regulate neuroinflammation and control amyloid plaque formation in Alzheimer’s disease mouse models.

A major research effort of my laboratory centers on the role of the cholesterol related genes in Alzheimer’s disease pathogenesis. We have identified SR-BI, the HDL cholesterol receptor, and LDLR, the LDL cholesterol receptor, as major modulators of neuroinflammation and amyloid plaque deposition in mouse models of the disease. Our results have provided unexpected evidence that these proteins might have a dual independent function in cholesterol transport and neuroinflammation and have led us to a novel concept for their role in Alzheimer’s disease pathogenesis. Furthermore we have identified macrophages/microglia as the cellular component involved in this process. Our current research efforts try to further elucidate the molecular and cellular mechanisms employed and identify novel therapeutic targets as SR-BI and LDLR in Alzheimer’s disease.

These data have guided us to investigate the contribution of TNF-a, a major inflammatory modulator, involved in macrophage/microglia activation, in Alzheimer’s disease pathogenesis. Using transgenic mouse models of disease we examine for a possible connection between Alzheimer’s disease and other pathologies where TNF-a is involved as rheumatoid arthritis. Combining transgenic mice of Alzheimer’s disease and rheumatoid arthritis we are searching for the possible common role of TNF-a in both diseases and evaluating the current therapeutic approaches for rheumatoid arthritis that target TNF-a, in Alzheimer’s disease.

Taken together our studies have generated a new concept where “old” molecules, like the cholesterol receptors or TNF-a, already related with certain pathologies as cardiovascular disease and rheumatoid arthritis, can have new different roles in illnesses like Alzheimer’s disease. This perspective can help to elucidate the riddle of Alzheimer’s disease and identify new “old” therapeutical targets.