β-Amyloid impairs axonal BDNF retrograde trafficking.
Wayne W. Poon,Mathew Blurton-Jones,Christina H. Tu,Leila M. Feinberg,Meredith A. Chabrier,Joseph Harris,Noo Li Jeon,Carl W. Cotman +7 more
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TLDR
A novel microfluidic culture chamber is used to demonstrate a BDNF retrograde signaling deficit in AD transgenic mouse neurons that can be reversed by γ-secretase inhibitors and shows that BDNF-mediated TrkB retrograde trafficking is impaired in Tg2576 axons.About:
This article is published in Neurobiology of Aging.The article was published on 2011-05-01 and is currently open access. It has received 180 citations till now. The article focuses on the topics: Tropomyosin receptor kinase B & Brain-derived neurotrophic factor.read more
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Protein aggregation diseases: pathogenicity and therapeutic perspectives
Adriano Aguzzi,Tracy O'Connor +1 more
TL;DR: It is now clear that ordered aggregation of pathogenic proteins does not only occur in the extracellular space, but in the cytoplasm and nucleus as well, indicating that many other diseases may also qualify as amyloidoses.
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Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain.
TL;DR: It is proposed that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.
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The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
TL;DR: If the momentum of AβO research continues, particularly efforts to elucidate key aspects of structure, a clear path to a successful disease modifying therapy can be envisioned, and lessons learned from recent, late-stage clinical failures are applied appropriately throughout therapeutic development will further enable the likelihood of a successful therapy in the near-term.
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Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease.
TL;DR: Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signalling) have been effective in animal models and in preliminary studies in humans.
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The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease.
TL;DR: Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms, including relationships to diabetes and Fragile X.
References
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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.
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Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo.
Dominic M. Walsh,Igor Klyubin,Julia V. Fadeeva,William K. Cullen,Roger Anwyl,Michael S. Wolfe,Michael J. Rowan,Dennis J. Selkoe +7 more
TL;DR: It is reported that natural oligomers of human Aβ are formed soon after generation of the peptide within specific intracellular vesicles and are subsequently secreted from the cell, indicating that synaptotoxic Aβ oligomers can be targeted therapeutically.
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Triple-Transgenic Model of Alzheimer's Disease with Plaques and Tangles: Intracellular Aβ and Synaptic Dysfunction
Salvatore Oddo,Antonella Caccamo,Jason D. Shepherd,M. Paul Murphy,Todd E. Golde,Rakez Kayed,Raju Metherate,Mark P. Mattson,Yama Akbari,Frank M. LaFerla +9 more
TL;DR: The recapitulation of salient features of AD in these mice clarifies the relationships between Abeta, synaptic dysfunction, and tangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.
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Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins
Mary P. Lambert,A. K. Barlow,Brett A. Chromy,C. Edwards,R. Freed,M. Liosatos,Todd E. Morgan,Irina Rozovsky,Barbara L. Trommer,Kirsten L. Viola,Pat Wals,Chuan Zhang,Caleb E. Finch,Grant A. Krafft,William L. Klein +14 more
TL;DR: It is hypothesized that impaired synaptic plasticity and associated memory dysfunction during early stage Alzheimer's disease and severe cellular degeneration and dementia during end stage could be caused by the biphasic impact of Abeta-derived diffusible ligands acting upon particular neural signal transduction pathways.
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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.