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Ovsepian, S.V. ; O'Leary, V.B.* ; Zaborszky, L.* ; Ntziachristos, V. ; Dolly, J.O.*

Amyloid plaques of Alzheimer’s disease as hotspots of glutamatergic activity.

Neuroscientist 25, 288-297 (2018)
Postprint DOI PMC
Open Access Green
Deposition of amyloid plaques in limbic and associative cortices is amongst the most recognized histopathologic hallmarks of Alzheimer’s disease. Despite decades of research, there is a lack of consensus over the impact of plaques on neuronal function, with their role in cognitive decline and memory loss undecided. Evidence has emerged suggesting complex and localized axonal pathology around amyloid plaques, with a significant fraction of swellings and dystrophies becoming enriched with putative synaptic vesicles and presynaptic proteins normally colocalized at hotspots of transmitter release. In the absence of hallmark active zone proteins and postsynaptic receptive elements, the axonal swellings surrounding amyloid plaques have been suggested as sites for ectopic release of glutamate, which under reduced clearance can lead to elevated local excitatory drive. Throughout this review, we consider the emerging data suggestive of amyloid plaques as hotspots of compulsive glutamatergic activity. Evidence for local and long-range effects of nonsynaptic glutamate is discussed in the context of circuit dysfunctions and neurodegenerative changes of Alzheimer’s disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Alzheimer’s Disease ; Axonal Dystrophies ; Ectopic Release ; Glutamate ; Metabotropic Receptors ; Paracrine Signaling
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 1073-8584
e-ISSN 1089-4098
Quellenangaben Volume: 25, Issue: 4, Pages: 288-297 Article Number: , Supplement: ,
Publisher Sage
Publishing Place Thousand Oaks, Calif.
Reviewing status Peer reviewed
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505500-001
Scopus ID 85052516257
PubMed ID 30051750
Erfassungsdatum 2018-08-01