Fig. 4

Experimental design for the discovery of genetic factors influencing cognitive resilience to amyloidosis. This study analyzed older individuals with significant brain amyloidosis and found evidence for genetic factors associated with cognitive resilience in that setting (green check mark). Alternative potential mediators for resilience were assessed, including intellectual enrichment, sex-related factors, resistance to tau accumulation, and cerebrovascular disease burden, and not explanatory for the genetic associations (red backslash icon). Our findings nominate new targets which warrant further study of the underlying molecular processes which impact brain structure and metabolism, functional network connectivity, and neuronal and synaptic health, to ultimately account for differential coping with amyloid pathology