Table 1.

Summary of aging-induced BBB damage in AD, PD, stroke and the underlying mechanisms.

Ref.	Neurological diseases	Species	BBB changes	Possible mechanisms
Barisano et al., 202234	Alzheimer's disease	Human	Loss of tight junction (TJ) or adherence junction (AJ) and increased transendothelial translocation	Associated with the loss of pericyte coverage
Zhang et al., 202038	Alzheimer's disease	Human	Increase of BBB permeability	APOE4 can catabolize BBB integrity by activating the MMP9 pathway in pericytes and endothelial cells
Lan et al., 202239	Parkinson's disease	Mouse	Reduce of tight junction proteins	Elevated levels of VEGFA and iNOS
Ruan et al., 202238	Parkinson's disease	Mouse	Loss of endothelial integrity of the brain	Microglia-mediated activation of matrix metalloproteinase-2 and 9
Kortekaas et al., 200540	Parkinson's disease	Human	Decrease of P-gp function	PD patients carry the 1T allele of the MDR3435 gene
Rite et al., 200741	Parkinson's disease	Mouse	Increase of BBB permeability	Inflammatory response and activation of astroglia
Candelario-Jalil et al., 202242	Ischemic stroke	Mouse	Endothelial dysfunction	Increased MMP, oxidative stress burst, microglia activation and peripheral immune cell infiltration
Phillips et al., 202331	Ischemic stroke	Mouse	Persistent BBB dysfunction with increased permeability of the paracellular barrier	DNA methylation
Alvarez et al., 201145	Multiple sclerosis	Human and mouse	Reduced expression of TJ and AJ proteins	Immune cell infiltration and upregulation of pro-inflammatory cytokines