Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

Table 1

Key structural and functional differences between the three main human APOE isoforms.

Description	E2	E3	E4
Primary sequence difference	C112	C112	R112
	C158	R158	R158
Structure particularity	Disruption of salt bridge network in the NT domain		Domain interaction (creation of salt bridges R112-E109 and R61-E255)
LDLR binding	<2% normal receptor binding activity	High	High
Lipoprotein binding	HDL	HDL	VLDL/LDL
Protein stability	+++	++	+
Molten-like-globule propensity	+	++	+++

E: glutamate; C: cysteine; R: arginine; LDLR: low-density lipoprotein receptor; HDL: high-density lipoprotein; VLDL: very-low-density lipoprotein; +/++/+++, respectively, low/medium/high.