Dr. Mazahir T. Hasan, Ikerbasque Research Professor at the Achucarro Basque Center for Neuroscience, located at the Scientific Park of the UPV/EHU in Leioa (Bizkaia, Spain) has been awarded one of the highly competitive National Institute of Health (NIH) R21 grant, funded with a total of USD 390,000.

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The National Institute for Aging is part of the NIH network of research centers in the US, and the funding agency for this R21 grant, which main objective is to test if genetically enhanced cholesterol biosynthesis in astrocytes and neurons can reverse the Alzheimer's disease (AD).  This project will be developed in collaboration with the laboratory of Dr. Ta-Yuan Chang at Dartmouth College (New Hampshire, USA).

Alzheimer's disease (AD) is a chronic neurodegenerative disease and a type of dementia. The most common early symptom is the short-term memory loss, the difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, and loss of motivation, not managing self-care, and behavioral issues. In AD, the accumulation of beta-amyloid plaques, the key culprit, disrupts cellular communication and connectivity in the brain by disrupting astrocytic calcium signaling and gliotransmitter release.

Cholesterol is important for brain functions, regulating dynamics membrane trafficking to cellular signaling systems, within and between cells. Even though brain represents only 2-3% of total body weight, roughly 25% of body cholesterol is found in the brain. Cholesterol is the building block of different steroid hormones, such as progesterone, estrogen, cortisol, testosterone and vitamin D. Malfunction in brain cholesterol homeostasis can have detrimental effects on brain connectivity, especially communication between astrocytes and neurons. Because dietary cholesterol cannot cross the blood-brain-barrier, our project aims to overcome this problems by genetic control of cholesterol synthesis in neurons and astrocytes, with an expectation that this would help to cure the Alzheimer's disease.