Amyloid-β-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype

Marcel M. Verbeek, William E. Van Nostrand, Irene Otte-Höller, Pieter Wesseling, Robert M.W. De Waal

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

34 Citaten (Scopus)

Samenvatting

Amyloid-β (Aβ) deposition in cerebral vessels (cerebral amyloid angiopathy, CAA) is accompanied by degeneration of vascular cells, including pericytes and smooth muscle cells. Previous studies indicated that specific Aβ protein isoforms are toxic for cultured human brain pericytes and smooth muscle cells. In particular, Aβ1-40 carrying the E22Q mutation, as in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), is toxic. We investigated the effects of the Aβ-binding protein apolipoprotein E (ApoE) on the toxicity of Aβ for cultured human brain pericytes, We compared the toxicity of HCHWA-D Aβ1-40 for pericyte cultures with different ApoE genotypes, studied the accumulation of Aβ and ApoE in these different cell cultures, and investigated the effects of exogenous ApoE, Pericyte cultures with an ApoE ε2/ε3 genotype were more resistant to HCHWA-D Aβ1-40 treatment than cultures with a ε3/ε3 or ε3/ε4 genotype. Cell death was highest in cultures homozygous for ApoE ε4, The extent to which both Aβ and ApoE accumulated at the cell surface was parallel to the degree of toxicity. The addition of purified ApoE resulted In a decrease in cell death. These data suggest that ApoE4 may direct Aβ more efficiently than other ApoE isoforms into a pathological interaction with the HBP cell surface. The results of this study are in line with the observations that inheritance of the ApoE ε4 allele increases the risk of developing Alzheimer's disease, and that the ApoE ε2 allele has a relatively protective effect.

Originele taal-2Engels
Pagina's (van-tot)187-199
Aantal pagina's13
TijdschriftAnnals of the New York Academy of Sciences
Volume903
DOI's
StatusGepubliceerd - 2000
Extern gepubliceerdJa

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