Journal ArticleDOI
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Christopher Janus,Jacqueline Pearson,JoAnne McLaurin,Paul M. Mathews,Ying Jiang,Stephen D. Schmidt,M. Azhar Chishti,Patrick Horne,Donna Heslin,Janet French,Howard T.J. Mount,Ralph A. Nixon,Marc Mercken,Catherine Bergeron,Catherine Bergeron,Paul E. Fraser,Peter St George-Hyslop,Peter St George-Hyslop,David Westaway +18 more
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TLDR
Aβ immunization reduces both deposition of cerebral fibrillar Aβ and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of Aβ in the brain, which implies that either a ∼50% reduction in dense-cored Aβ plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic Aβ species.Abstract:
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-β peptide (Aβ), a proteolytic derivative of the β-amyloid precursor protein (βAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with Aβ causes a marked reduction in burden of the brain amyloid2,3. Evidence that Aβ immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal Aβ processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the ‘amyloid cascade’. Here we show that Aβ immunization reduces both deposition of cerebral fibrillar Aβ and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of Aβ in the brain. This implies that either a ∼50% reduction in dense-cored Aβ plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic Aβ species.read more
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Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
Christian Haass,Dennis J. Selkoe +1 more
TL;DR: Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.
Journal ArticleDOI
Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.
TL;DR: Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging.
Journal ArticleDOI
A specific amyloid-|[beta]| protein assembly in the brain impairs memory
Sylvain Lesné,Ming Teng Koh,Linda Kotilinek,Rakez Kayed,Charles G. Glabe,Austin J. Yang,Michela Gallagher,Karen H. Ashe +7 more
TL;DR: It is found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-β assembly, which is proposed to be Aβ*56 (Aβ star 56), which may contribute to cognitive deficits associated with Alzheimer's disease.
Journal ArticleDOI
TREM2 Variants in Alzheimer's Disease
Rita Guerreiro,Rita Guerreiro,Aleksandra Wojtas,Jose Bras,Minerva M. Carrasquillo,Ekaterina Rogaeva,Elisa Majounie,Carlos Cruchaga,Celeste Sassi,Celeste Sassi,John S. K. Kauwe,Steven G. Younkin,Lili-Naz Hazrati,John Collinge,Jennifer M. Pocock,Tammaryn Lashley,Julie Williams,Jean-Charles Lambert,Philippe Amouyel,Alison Goate,Rosa Rademakers,Kevin Morgan,John Powell,Peter St George-Hyslop,Peter St George-Hyslop,Andrew B. Singleton,John Hardy +26 more
TL;DR: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease.
Journal ArticleDOI
Intracellular amyloid-β in Alzheimer's disease
TL;DR: Although the classical view is that Aβ is deposited extracellularly, emerging evidence from transgenic mice and human patients indicates that this peptide can also accumulate intraneuronally, which may contribute to disease progression.
References
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Journal ArticleDOI
Developments of a water-maze procedure for studying spatial learning in the rat
TL;DR: Developments of an open-field water-maze procedure in which rats learn to escape from opaque water onto a hidden platform are described, suggesting that they may lend themselves to a variety of behavioural investigations, including pharmacological work and studies of cerebral function.
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
Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.
Dale Schenk,Robin Barbour,Whitney Dunn,Grace Gordon,Henry Grajeda,Teresa Guido,Kang Hu,Jiping Huang,Kelly Johnson-Wood,Karen Khan,Dora Kholodenko,Michael K. Lee,Zhenmei Liao,Ivan Lieberburg,Ruth Motter,Linda Mutter,Ferdie Soriano,George Shopp,Vasquez Nicki J,Christopher Vandevert,Shannan Walker,Mark Wogulis,Ted Yednock,Dora Games,Peter Seubert +24 more
TL;DR: It is reported that immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis, and treatment of the older animals markedly reduced the extent and progression of these AD-like neuropathologies.
Journal ArticleDOI
Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.
Frederique Bard,Catherine Cannon,Robin Barbour,Rae Lyn Burke,Dora Games,Henry Grajeda,Teresa Guido,Kang Hu,Jiping Huang,Kelly Johnson-Wood,Karen Khan,Dora Kholodenko,Michael K. Lee,Ivan Lieberburg,Ruth Motter,Minh Nguyen,Ferdie Soriano,Vasquez Nicki J,Kim Weiss,Brent Welch,Peter Seubert,Dale Schenk,Ted Yednock +22 more
TL;DR: Results indicate that antibodies can cross the blood–brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.
Journal ArticleDOI
Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease.
Catriona McLean,Robert A. Cherny,Fiona W. Fraser,Stephanie J. Fuller,Margaret J. Smith,Konrad Beyreuther,Ashley I. Bush,Ashley I. Bush,Colin L. Masters +8 more
TL;DR: The genetic evidence strongly supports the view that Aβ amyloid production is central to the cause of Alzheimer's disease, and the concept of several interacting pools of Aβ, that is, a large relatively static insoluble pool that is derived from a constantly turning over smaller soluble pool, is supported.
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