Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice
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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.
in: MOL PSYCHIATR, Jahrgang 18, Nr. 3, 01.03.2013, S. 358-68.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Active vaccination with ankyrin G reduces β-amyloid pathology in APP transgenic mice
AU - Santuccione, A C
AU - Merlini, M
AU - Shetty, A
AU - Tackenberg, C
AU - Bali, J
AU - Ferretti, M T
AU - McAfoose, J
AU - Kulic, L
AU - Bernreuther, C
AU - Welt, T
AU - Grimm, J
AU - Glatzel, M
AU - Rajendran, L
AU - Hock, C
AU - Nitsch, R M
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
AB - 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.
KW - Alzheimer Disease
KW - Amyloid beta-Peptides
KW - Animals
KW - Ankyrins
KW - Antibodies
KW - Antibodies, Monoclonal
KW - Brain
KW - Cells, Cultured
KW - Hippocampus
KW - Humans
KW - Mice
KW - Mice, Transgenic
KW - Neurons
KW - Peptide Fragments
KW - Plaque, Amyloid
KW - Vaccination
U2 - 10.1038/mp.2012.70
DO - 10.1038/mp.2012.70
M3 - SCORING: Journal article
C2 - 22688190
VL - 18
SP - 358
EP - 368
JO - MOL PSYCHIATR
JF - MOL PSYCHIATR
SN - 1359-4184
IS - 3
ER -