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Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology
Ina Tesseur, … , Eliezer Masliah, Tony Wyss-Coray
Ina Tesseur, … , Eliezer Masliah, Tony Wyss-Coray
Published November 1, 2006
Citation Information: J Clin Invest. 2006;116(11):3060-3069. https://doi.org/10.1172/JCI27341.
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Research Article Neuroscience Article has an altmetric score of 16

Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology

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Abstract

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and cerebral accumulation of the β-amyloid peptide (Aβ), but it is unknown what makes neurons susceptible to degeneration. We report that the TGF-β type II receptor (TβRII) is mainly expressed by neurons, and that TβRII levels are reduced in human AD brain and correlate with pathological hallmarks of the disease. Reducing neuronal TGF-β signaling in mice resulted in age-dependent neurodegeneration and promoted Aβ accumulation and dendritic loss in a mouse model of AD. In cultured cells, reduced TGF-β signaling caused neuronal degeneration and resulted in increased levels of secreted Aβ and β-secretase–cleaved soluble amyloid precursor protein. These results show that reduced neuronal TGF-β signaling increases age-dependent neurodegeneration and AD-like disease in vivo. Increasing neuronal TGF-β signaling may thus reduce neurodegeneration and be beneficial in AD.

Authors

Ina Tesseur, Kun Zou, Luke Esposito, Frederique Bard, Elisabeth Berber, Judith Van Can, Amy H. Lin, Leslie Crews, Patrick Tremblay, Paul Mathews, Lennart Mucke, Eliezer Masliah, Tony Wyss-Coray

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Figure 1

TβRII protein levels are decreased in the human AD brain.

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TβRII protein levels are decreased in the human AD brain.
(A) Representa...
(A) Representative immunoblots of lysates from AD and age-matched control (Con) parietal corteices probed with antibodies against TβRII, actin, and neuron-specific enolase (NSE). (B) TβRII levels of nondemented control, AD, Parkinson’s disease (PD), progressive frontotemporal dementia (FTD), lewy body dementia (LB), progressive supranuclear palsy (PSP), and Pick’s disease (Pick’s) cases were quantified and normalized against protein amounts loaded. Each symbol represents an individual case. (C) TβRII protein levels grouped per mini-mental state exam (MMSE) score (white bar, nondemented controls; black bars, AD). (D and E) TβRII immunofluorescence localized to neurons in the mid-frontal gyrus of the brain from a 69-year-old human (D) and the cortex of a 3-month-old wild-type mouse (E). (F) Little TβRII staining localized to astrocytes in the mouse brain. Scale bars: 10 μm. **P < 0.05, ***P < 0.005; Student’s t test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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