Table 1.

Cells of the BBB in aging, Alzheimer’s disease (AD), and vascular dementia (VaD). (BBB: blood–brain barrier, AD: Alzheimer’s disease, VaD: vascular dementia, and N/A: not applicable).

Cells	Disease	Cell Number	Phenotype	Reference
Pericyte	Aged mice	Decrease	BBB degradation	[27]
	Aged mice	Decrease	BBB reduction	[43]
	Aged brain	Decrease	Cell numbers decreased in the BBB	[44]
	Aged brain	Decrease	Cell numbers decreased in the BBB	[111]
	Aged monkeys	Unchanged	Cell numbers unchanged	[45]
	AD	Decrease	Amyloid beta and p-tau proteins increased	[47]
	AD	Decrease	BBB degradation	[111]
	Aged rats	Increase	Cell numbers increased	[44]
	VaD	Decrease	Pericyte dysfunction	[49]
Astrocyte	Aging	N/A	BBB dysfunction	[54]
	Aging	N/A	CLDN5 and OCLN increased	[58]
	Aging	N/A	CLDN5 and OCLN increased	[57]
	Aging	N/A	TJ proteins, claudin-5, and occludin decreased	[62]
	KO mice (deletion of astrocytic laminin)	N/A	Loss in TJs in ECs	[52]
	AD brain	N/A	BBB breakdown	[47]
	AD brain	N/A	Depolarization of astrocyte terminals	[59]
	AD	N/A	Morphological changes in astrocyte ends	[60]
	VaD	Cell activation	Brain injury, lipid peroxidation, and neuronal death	[61]
Microglia	Aging /neurodegenerative diseases	N/A	Microglia activated	[62]
	Aging /neurodegenerative disease	N/A	Became an amoeba or phagocytic morphology	[64]
	Aging /neurodegenerative disease	N/A	Leakage of the BBB	[10]
	Aging	N/A	BBB collapsed	[69]
	Aging	N/A	BBB collapsed	[70]
	Altered microglia morphology	N/A	BBB integrity compromised	[72]
	AD brain	N/A	Secrete inflammatory cytokines by microglia	[73]
	AD brain	N/A	BBB damage	[74]
	Hypertension	Cell activation	Increased permeability of the blood–brain barrier (BBB)	[76]
Neuron	Production of reactive oxygen species	N/A	BBB dysfunction	[74]
	Production of reactive oxygen species	N/A	Neurodegeneration	[67]
	BBB integrity compromised	N/A	Fibrin aggregates in the brain	[79]
	Accumulation of fibrin in the brain	Decrease	Cause damage to neuronal axons	[80]
	VaD	Increase	The number of DCX-positive neurons increases	[81]
Endothelial cells	Plasmin activate MMPs	Decrease	Degradation of TJs and basal lamina	[94]
	CNS damage/BBB dysfunction	Decrease	ECs release complement regulatory proteins, which infiltrate the brain	[85]
	Produced C3a and C5a binding to C3aR and C5aR1	N/A	Infiltration of inflammatory cells into the brain	[86]
	Produced C3a and C5a binding to C3aR and C5aR1	N/A	Cytokine cascade	[87]
	AD	N/A	Beta-amyloid (Aβ) activates complement signaling by binding to C1q	[88]
	AD	N/A	Inhibition of the C5/C5aR1 pathway protects against damage	[88]
	Cognitive impairment	N/A	Increased ICAM-1 and VCAM-1 in vascular ECs in CCH	[97]
	VaD	Decrease	Express genes associated with programmed cell death	[98]
Oligodendrocyte	Damage to oligodendrocytes	N/A	Inhibition of remyelination	[99]
	Hypoxia, oxidative stress, and inflammation	N/A	Cognitive impairment	[101]
	SVD	N/A	Block oligodendroglial differentiation	[103]
Macrophage	Perivascular macrophages (PVMs)	N/A	Reduce vascular leakage	[105]
	PVMs	N/A	Lower pathogens	[105]
	PVMs	N/A	Limit inflammation	[105]
	PVMs	N/A	Remove toxin products from the brain parenchyma	[106]
	Deficiency of CD36 and Nox2 in macrophage	N/A	Inhibited ROS production	[106]
	AD	N/A	M2b macrophage subset decrement and M1 macrophage subset increment	[107]
Fibroblast (FB)	AD	N/A	Phagocytose and alleviate Aβ plaques	[105]
	Zebrafish lacking col5a1,	N/A	Under genetic ablation of the col1a2 gene, additional spontaneous bleeding	[110]
	Aβ aggregation and AD	N/A	Damage to FBs around blood vessels, leads to the dysregulation of AQP4	[109]
	Neurological disorders	N/A	Altered activity of perivascular FBs	[108]