Low expression of PDGFR-β impairs the blood-brain barrier and accelerates cellular aging in the hippocampal region

Alzheimer's disease (AD) is a chronic neurodegenerative disorder primarily affecting the elderly, leading to cognitive decline, memory impairment, and compromised daily functioning. There is a complex interplay between vascular pathology and AD pathogenesis: vascular dysfunction can reduce cerebral blood flow and alter blood-brain barrier (BBB) permeability, thereby promoting neurodegeneration, while hallmark AD pathologies (such as Aβ deposition and tau tangles) can also impair vascular integrity. Pericytes play a crucial role in maintaining capillary integrity and BBB function, with PDGFR-β (platelet-derived growth factor receptor beta) serving as one of their specific markers. However, its role in AD pathogenesis remains incompletely understood. This study constructed a Pdgfr-β knockdown mouse model (Pdgfr-β+/- mice) to analyze its effects on cerebrovascular pericyte coverage, BBB function, and brain aging. The study found that Pdgfr-β knockdown led to a reduction in cerebrovascular pericytes in mice. Additionally, Pdgfr-β+/- mice exhibited decreased expression of BBB tight junction proteins, damage to the vascular basement membrane, increased BBB permeability, and accelerated cellular senescence in the hippocampus. The results demonstrate that Pdgfr-β plays a critical role in maintaining BBB function and cerebrovascular health, and its reduced expression may accelerate brain aging processes.