ISSN:
1420-9071
Keywords:
Key Words. Apolipoprotein E (apoE); Alzheimer’s disease (AD); amyloid β protein (Aβ); apoE receptor; high-density lipoprotein (HDL).
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract. Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s000180050428
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