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Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.
J Alzheimers Dis. 2012; 31(2):359-69.JA

Abstract

Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where the ε4 allele increases and the ε2 allele decreases the risk for developing disease. Specific mutations within the amyloid-β (Aβ) peptide have been identified that cause familial forms of CAA. However, the influence of APOE genotype on accumulation of CAA mutant Aβ in brain is not well understood. Earlier, we showed that human ApoE4 redistributes fibrillar amyloid deposition from the cerebral microvasculature to parenchymal plaques in Tg-SwDI mice, a model that accumulates human Dutch/Iowa (E22Q/D23N) CAA mutant Aβ in brain (Xu et al., J Neurosci 28, 5312-5320, 2008). Human ApoE2 can reduce Aβ pathology in transgenic models of parenchymal plaques. Here we determined if human ApoE2 can influence the location and severity of amyloid pathology in Tg-SwDI mice. Comparing Tg-SwDI mice bred onto a human APOE2/2 or human APOE4/4 background, we found there was no change in the brain levels of total Aβ(40) and Aβ(42) compared to mice on the endogenous mouse APOE background. In Tg-SwDI mice on either human APOE background, there was a similarly strong reduction in the levels of microvascular CAA and emergence of extensive parenchymal plaque amyloid. In both Tg-SwDI-hAPOE2/2 and Tg-SwDI-hAPOE4/4 mice, the distribution of ApoE proteins and neuronal loss were associated with parenchymal amyloid plaques. These findings suggest that compared with human ApoE4, human ApoE2 does not beneficially influence the quantitative or spatial accumulation of human Dutch/Iowa CAA mutant amyloid or associated pathology in transgenic mice.

Authors+Show Affiliations

Department of Neurosurgery and Medicine, Stony Brook University, Stony Brook, NY 11794-8122, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22635103

Citation

Xu, Feng, et al. "Human Apolipoprotein E2 Promotes Parenchymal Amyloid Deposition and Neuronal Loss in Vasculotropic Mutant Amyloid-β Protein Tg-SwDI Mice." Journal of Alzheimer's Disease : JAD, vol. 31, no. 2, 2012, pp. 359-69.
Xu F, Vitek MP, Colton CA, et al. Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. J Alzheimers Dis. 2012;31(2):359-69.
Xu, F., Vitek, M. P., Colton, C. A., Previti, M. L., Davis, J., & Van Nostrand, W. E. (2012). Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. Journal of Alzheimer's Disease : JAD, 31(2), 359-69. https://doi.org/10.3233/JAD-2012-120421
Xu F, et al. Human Apolipoprotein E2 Promotes Parenchymal Amyloid Deposition and Neuronal Loss in Vasculotropic Mutant Amyloid-β Protein Tg-SwDI Mice. J Alzheimers Dis. 2012;31(2):359-69. PubMed PMID: 22635103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. AU - Xu,Feng, AU - Vitek,Michael P, AU - Colton,Carol A, AU - Previti,Mary Lou, AU - Davis,Judianne, AU - Van Nostrand,William E, PY - 2012/5/29/entrez PY - 2012/5/29/pubmed PY - 2013/6/5/medline SP - 359 EP - 69 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 31 IS - 2 N2 - Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where the ε4 allele increases and the ε2 allele decreases the risk for developing disease. Specific mutations within the amyloid-β (Aβ) peptide have been identified that cause familial forms of CAA. However, the influence of APOE genotype on accumulation of CAA mutant Aβ in brain is not well understood. Earlier, we showed that human ApoE4 redistributes fibrillar amyloid deposition from the cerebral microvasculature to parenchymal plaques in Tg-SwDI mice, a model that accumulates human Dutch/Iowa (E22Q/D23N) CAA mutant Aβ in brain (Xu et al., J Neurosci 28, 5312-5320, 2008). Human ApoE2 can reduce Aβ pathology in transgenic models of parenchymal plaques. Here we determined if human ApoE2 can influence the location and severity of amyloid pathology in Tg-SwDI mice. Comparing Tg-SwDI mice bred onto a human APOE2/2 or human APOE4/4 background, we found there was no change in the brain levels of total Aβ(40) and Aβ(42) compared to mice on the endogenous mouse APOE background. In Tg-SwDI mice on either human APOE background, there was a similarly strong reduction in the levels of microvascular CAA and emergence of extensive parenchymal plaque amyloid. In both Tg-SwDI-hAPOE2/2 and Tg-SwDI-hAPOE4/4 mice, the distribution of ApoE proteins and neuronal loss were associated with parenchymal amyloid plaques. These findings suggest that compared with human ApoE4, human ApoE2 does not beneficially influence the quantitative or spatial accumulation of human Dutch/Iowa CAA mutant amyloid or associated pathology in transgenic mice. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22635103/Human_apolipoprotein_E2_promotes_parenchymal_amyloid_deposition_and_neuronal_loss_in_vasculotropic_mutant_amyloid_β_protein_Tg_SwDI_mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-120421 DB - PRIME DP - Unbound Medicine ER -