Journal ArticleDOI
Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease
Tony Wyss-Coray,Eliezer Masliah,Margaret Mallory,Lisa McConlogue,Kelly Johnson-Wood,Carol Lin,Lennart Mucke +6 more
TLDR
It is reported that TGF-β1 induces amyloid-β deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes, and so may be a risk factor for developing Alzheimer's disease.Abstract:
Deposition of amyoid-beta peptide in the central nervous system is a hallmark of Alzheimer's disease and a possible cause of neurodegeneration. The factors that initiate or promote deposition of amyloid-beta peptide are not known. The transforming growth factor TGF-beta1 plays a central role in the response of the brain to injury, and increased TGF-beta1 has been found in the central nervous system of patients with Alzheimer's disease. Here we report that TGF-beta1 induces amyloid-beta deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes. Co-expression of TGF-beta1 in transgenic mice overexpressing amyloid-precursor protein, which develop Alzheimer's like pathology, accelerated the deposition of amyloid-beta peptide. More TGF-beta1 messenger RNA was present in post-mortem brain tissue of Alzheimer's patients than in controls, the levels correlating strongly with amyloid-beta deposition in the damaged cerebral blood vessels of patients with cerebral amyloid angiopathy. These results indicate that overexpression of TGF-beta1 may initiate or promote amyloidogenesis in Alzheimer's disease and in experimental models and so may be a risk factor for developing Alzheimer's disease.read more
Citations
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Journal ArticleDOI
Inflammation and Alzheimer's disease.
Haruhiko Akiyama,Steven W. Barger,Scott R. Barnum,B Bradt,Jürgen Bauer,Greg M. Cole,Neil R. Cooper,Piet Eikelenboom,Mark R. Emmerling,Bernd L. Fiebich,Caleb E. Finch,Sally A. Frautschy,W. S. T. Griffin,Harald Hampel,Michael Hüll,Gary E. Landreth,Lih-Fen Lue,Robert E. Mrak,Ian R. A. Mackenzie,Patrick L. McGeer,M K O'Banion,Joel S. Pachter,Giulio Maria Pasinetti,C Plata-Salaman,Joseph G. Rogers,Russell E. Rydel,Yueyang Shen,Wolfgang J. Streit,Ronald Strohmeyer,I Tooyoma,F L van Muiswinkel,R. Veerhuis,David G. Walker,Scott D. Webster,Beatrice Hauss–Wegrzyniak,Gary L. Wenk,Tony Wyss-Coray +36 more
TL;DR: By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.
Journal ArticleDOI
High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation.
Lennart Mucke,Eliezer Masliah,Gui-Qiu Yu,Margaret Mallory,Edward Rockenstein,Gwen Tatsuno,Kang Hu,Dora Kholodenko,Kelly Johnson-Wood,Lisa McConlogue +9 more
TL;DR: It is concluded that Aβ is synaptotoxic even in the absence of plaques and that high levels of Aβ1–42 are insufficient to induce plaque formation in mice expressing wild-type hAPP, supporting the emerging view that plaque-independent Aβ toxicity plays an important role in the development of synaptic deficits in AD and related conditions.
Journal ArticleDOI
Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models.
Albert Y. Hsia,Eliezer Masliah,Lisa McConlogue,Gui Qiu Yu,Gwen Tatsuno,Kang Hu,Dora Kholodenko,Robert C. Malenka,Roger A. Nicoll,Lennart Mucke +9 more
TL;DR: It is shown that overexpression of FAD(717V-->F)-mutant human APP in neurons of transgenic mice decreases the density of presynaptic terminals and neurons well before these mice develop amyloid plaques, suggesting a neurotoxic effect of Abeta that is independent of plaque formation.
Journal ArticleDOI
Trace elements in human physiology and pathology: zinc and metallothioneins.
H Tapiero,Kenneth D. Tew +1 more
TL;DR: Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.
Journal ArticleDOI
Inflammation in Neurodegenerative Disease—A Double-Edged Sword
Tony Wyss-Coray,Lennart Mucke +1 more
TL;DR: Since many inflammatory responses are beneficial, directing and instructing the inflammatory machinery may be a better therapeutic objective than suppressing it.
References
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Journal ArticleDOI
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Karen Hsiao,Paul F. Chapman,Steven P. Nilsen,Chris Eckman,Yasuo Harigaya,Steven G. Younkin,Fusheng Yang,Greg M. Cole +7 more
TL;DR: Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer β-amyloid (Aβ) precursor protein containing a Lys670 → Asn, Met671 → Leu mutation had normal learning and memory but showed impairment by 9 to 10 months of age.
Journal ArticleDOI
Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
Dora Games,David S. Adams,Ree Alessandrini,Robin Barbour,Patricia Borthelette,Catherine Blackwell,Tony Carr,J. C. Clemens,Thomas Donaldson,Frances Gillespie,Terry Guido,Stephanie Hagopian,Kelly Johnson-Wood,Karen Khan,Michael K. Lee,Paul Leibowitz,Ivan Lieberburg,Sheila P. Little,Eliezer Masliah,Lisa McConlogue,Martin Montoya-Zavala,Lennart Mucke,Lisa Paganini,Elizabeth Penniman,Michael Power,Dale Schenk,Peter Seubert,Ben W. Snyder,Ferdie Soriano,Hua Tan,James Vitale,Sam Wadsworth,Ben Wolozin,Jun Zhao +33 more
TL;DR: Transgenic mice that express high levels of human mutant APP support a primary role for APP/Aβ in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Journal ArticleDOI
Amyloid, the presenilins and Alzheimer's disease
TL;DR: It is argued that genetic and molecular biological data provide strong support for the veracity of the 'amyloid cascade hypothesis' for disease pathogenesis, and that this hypothesis offers a coherent framework for drug discovery.
Journal ArticleDOI
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease
Donald E. Schmechel,Ann M. Saunders,Warren J. Strittmatter,Barbara J. Crain,Christine M. Hulette,S. H. Joo,Margaret A. Pericak-Vance,Dmitry Goldgaber,A. D. Roses +8 more
TL;DR: In an autopsy series of brains of late-onset AD patients, a strong association of APOE4 allele with increased vascular and plaque A beta deposits is found.
Journal ArticleDOI
The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases.
TL;DR: Multiple epidemiological studies indicate that patients taking anti-inflammatory drugs or suffering from conditions in which such drugs are routinely used, have a decreased risk of developing Alzheimer disease.
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