A new study published in the Acta Neuropathologica journal has identified a potential genetic link that connects Alzheimer’s disease with cardiovascular and cerebrovascular risk factors such as hypertension, obesity and diabetes.
Alzheimer’s disease, cardiovascular and cerebrovascular disease share similar risk factors that are linked to blood vessel dysfunction, such as hypertension, obesity and diabetes. In their new study, a team of researchers led by Richard Mayeux of Columbia University (New York, USA) identified a novel gene that may connect these risk factors to Alzheimer’s disease (AD). This gene, called FMNL2 (Formin-Like protein 2), was identified via a genome-wide screen of over 12,000 participants with a history of cardiovascular or cerebrovascular disease in the WHICAP, EFIGA, NACC and ROSMAP clinical studies, representing many different ethnic backgrounds. Analyses of post mortem brain samples donated by people with brain infarcts or AD revealed larger quantities of FMNL2 transcript in areas of the brain with AD or vascular pathology.
To understand how FMNL2 might influence the development of AD, the researchers then turned to animal models of disease. By manipulating the levels of FMNL2 in a zebrafish model, and by analysing the brains of AD mice, they found that increased FMNL2 was linked to abnormal brain blood vessels. Microscopic evaluation of brain samples revealed altered connections between astrocytes and vascular cells of the blood-brain barrier. Astrocytes help maintain the structure of the blood-brain barrier, and support the clearance of damaging proteins from the brain. Blocking FMNL2 in zebrafish led to defective clearance of toxic amyloid beta proteins from the brain, pointing to a potential biological role for FMNL2 in AD.
To read the orginal article: https://link.springer.com/article/10.1007/s00401-022-02431-6#Sec22
