We are glad to announce another preprint from our lab.
We have discovered rare genetic variations in a gene associated with the extracellular matrix (ECM) that might protect against Alzheimer’s disease for those at higher genetic risk, specifically individuals carrying the APOEe4 allele. The study used whole genome sequencing data from different cohorts to isolate these variants among elderly APOEe4 carriers who did not develop dementia. We found these variants, particularly in a gene called Fibronectin 1 (FN1), correlated with lower protein deposits at the blood-brain barrier and decreased reactive gliosis in unaffected carriers. Zebrafish models confirmed that loss of FN1 function could reduce brain damage in Alzheimer’s. This research suggests targeting ECM components could be a therapeutic strategy against Alzheimer’s.
Kizil Lab 