FunGen-AD research demonstrates the neuroprotective effect of the clusterin protein

The protein clusterin (CLU) was identified in Alzheimer’s disease (AD) nearly 30 years ago; however, its role in AD has not been established, particularly whether it is neuroprotective, pathogenic, or has another role. Most studies focused on CLU in AD have used mouse models or studied CLU’s role outside of the brain.A team of researchers, including FunGen-AD-funded investigator Philip De Jager from Columbia University, elucidated CLU’s mechanism in AD using a mouse model carrying a humanized CLU risk variant, human brain cell models of CLU deficiency, s, and brain tissue from over 700 participants of the Religious Orders Study and Memory and Aging Projects (ROSMAP) study.

Analyses of the ROSMAP tissue samples showed that CLU protein levels are elevated in AD. Experiments in the mouse and human cell models showed that those with CLU AD-associated SNPs showed reduced CLU expression, which was associated with increased inflammation and reduced neuronal synapses. These results support the hypothesis that increasing CLU in AD patients with amyloid plaques and tau tangles can prevent inflammatory signaling, protect against neurodegeneration, and reduce cognitive decline. Increasing CLU could also treat other age-related brain diseases that are affected by neuroinflammation. Overall, this study demonstrates the neuroprotective effect of CLU and provides compelling evidence to support designing and testing new therapies targeting CLU for AD.

This research, partially supported by FunGen-AD grant U01AG072572, is published in Neuron here. You can read more about these research findings at the following links: