Table 3.

Spatio‐temporal changes in the human brain's ECM in NDDs.

Brain ECM	Constituents	NDD	Spatio‐Temporal Dynamics in NDDs	Reference
Interstitial Matrix & PNN	HA	AD	↑ at the perimeter of plaques	[189]
		MS	↑ High‐MW HA accumulation in chronic lesions ↑ Low‐MW HA in acute lesions	[183, 190]
	Proteoglycans	AD	CSPGs present in neurofibrillary tangles and senile plaquesDSPGs associated with senile plaquesKSPGs located at synapses and neurites within plaquesDecorin associated with periphery of plaques and neurofibrillary tanglesHSPG Agrin ↑ around senile plaques and hyperphosphorylated tau Around senile plaques and neurofibrillary tangles glypican and syndecan ↑	[174, 191, 192, 193]
		PD	HSPG Accumulation of agrin in Lewy body Versican expression ↑	[194, 195]
		MS	Aggrecan, versican, neurocan, dermatan sulfate proteoglycans ↑ around lesions Aggrecan, versican, neurocan, dermatan sulfate proteoglycans ↓ in the center of lesions	[196]
	Glycoproteins	AD	Reelin ↓ Tenascin C associated with cored plaques Tenascin C & R significantly ↑ in CSF of female patients Thrombospondin‐1 ↓	[197, 198, 199, 200]
		MS	Tenascin C & R In MS lesions ↑ Around lesions ↓ Laminin ↑	[174, 201]
Basement Membrane	Collagen	AD	Collagen IV ↑ Collagen IV ↓ in AD neuropathological change	[178, 184, 202]
		ALS	Collagen IV ↑	[203]
		PD	Collagen I expression ↑ Collagen IV ↑	[195, 204]
	Fibronectin	AD	↑	[184, 205]
	Proteoglycans	AD	HSPGs ↑ Perlecan ↑	[184, 206]
	Glycoproteins	AD	Laminin Fragmentation ↑ ↓ in AD neuropathological change Nidogen ↓Agrin ↑	[184, 202, 205, 207, 208, 209, 210, 211]
		ALS	Laminin ↑	[212, 213]