Loss of large dendritic spines during normal aging is mediated by alterations in discrete protein networks within the precuneus

Loss of dendritic spine density in neocortical areas is a well‐known correlate of cognitive decline in Alzheimer Disease (AD), while preservation of dendritic spines in subjects containing AD‐related pathology is associated with cognitive resilience. Because normal aging is itself associated with dendritic spine loss, identifying upstream mediators of dendritic spine loss may provide an opportunity to develop targeted pharmacotherapies which enhance cognitive resilience and protect against dementia onset. We therefore quantified dendritic spine density and the abundance of over 5000 proteins in the precuneus, a cortical region that is selectively vulnerable early in AD progression.