Header

UZH-Logo

Maintenance Infos

Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice


Santuccione, A C; Merlini, M; Shetty, A; Tackenberg, C; Bali, J; Ferretti, M T; McAfoose, J; Kulic, L; Bernreuther, C; Welt, T; Grimm, J; Glatzel, M; Rajendran, L; Hock, C; Nitsch, R M (2013). Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice. Molecular Psychiatry, 18(3):358-368.

Abstract

Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in β-amyloid plaques. Active immunization with ankG of arcAβ transgenic mice reduced brain β-amyloid pathology and increased brain levels of soluble Aβ(42). AnkG immunization induced a reduction in β-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aβ-induced loss of dendritic spines in hippocampal ArcAβ organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain β-amyloid and its related neuropathology.

Abstract

Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in β-amyloid plaques. Active immunization with ankG of arcAβ transgenic mice reduced brain β-amyloid pathology and increased brain levels of soluble Aβ(42). AnkG immunization induced a reduction in β-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aβ-induced loss of dendritic spines in hippocampal ArcAβ organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain β-amyloid and its related neuropathology.

Statistics

Citations

13 citations in Web of Science®
15 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:14 Nov 2012 13:43
Last Modified:07 Dec 2017 16:14
Publisher:Nature Publishing Group
ISSN:1359-4184
Publisher DOI:https://doi.org/10.1038/mp.2012.70
PubMed ID:22688190

Download

Full text not available from this repository.
View at publisher