Overview
- A peer-reviewed study in Alzheimer’s & Dementia identifies degradation of perineuronal nets in hippocampal CA2 as the proximate driver of social memory deficits in 5XFAD mice.
- Mice with compromised nets failed to recognize familiar individuals while maintaining object memory, reflecting a pattern often observed in people with Alzheimer’s.
- Bulk RNA sequencing implicated elevated matrix metalloproteinases in net proteolysis, with genetic and enzymatic disruptions recapitulating the social-memory impairment.
- Chronic inhibition of matrix metalloproteinases preserved CA2 nets and delayed the onset of social-memory decline in the Alzheimer’s mouse model.
- The mechanism occurred independently of amyloid plaque pathology, and the authors emphasize that translation to human treatment requires further safety and efficacy studies.