Perineuronal Nets in the Pathophysiology of Alzheimer's Disease 126 views

Alzheimer’s disease (AD) affects approximately 55 million individuals globally and is the most prevalent form of dementia, characterized by profound impairments in memory and cognition that extend beyond normal aging. AD is a progressive neurodegenerative disorder in which subtle molecular and cellular alterations occur decades before the clinical manifestation of deficits in memory, language, and executive functions, ultimately leading to motor impairments such as difficulties in walking and swallowing. Current therapies remain largely limited to preventive and symptomatic interventions, underscoring the urgent need to identify novel and disease-modifying treatments. One of the devastating aspects of AD is the loss of social recognition memory, the ability to identify and respond to familiar individuals, including family members and friends. Emerging evidence indicates that alterations in the brain’s extracellular matrix (ECM) are associated with AD pathology and disease progression. Among the ECM components, perineuronal nets (PNNs) have gained attention as critical regulators of neuronal plasticity, synaptic stability, and memory processes. This dissertation investigates the role of PNNs in modulating social memory deficits in AD. We delineate the temporal dynamics of PNN degradation in an AD mouse model and demonstrate that timely inhibition of PNN breakdown mitigates the progression of social memory impairment. Collectively, our findings highlight the significance of ECM remodeling in AD and suggest that targeting PNN integrity may represent a promising therapeutic strategy for preserving cognitive and social memory functions in Alzheimer’s disease.

PHD (Doctor of Philosophy)

Alzheimer's Disease; extracellular matrix; perineuronal nets; social memory; ECM remodeling

English

2025-11-27