Amyloid Plaques of Alzheimer’s Disease as Hotspots of Glutamatergic Activity

Neuroscientist - Tập 25 Số 4 - Trang 288-297 - 2019
Saak V. Ovsepian1,2,3, Valerie B. O’Leary2, László Záborszky4, Vasilis Ntziachristos1,3, J. Oliver Dolly2
1Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany
2International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland
3Munich School of Bioengineering, Technical University Munich, Munich, Germany
4Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ, USA

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1007/BF00369449

10.1016/j.nbd.2005.05.001

10.1016/0304-3940(95)11796-Y

10.1007/s00401-010-0787-6

10.1073/pnas.1206171109

10.1126/science.1162844

10.1002/bies.201500004

10.1146/annurev.neuro.26.010302.081142

10.1016/S0028-3908(98)00123-3

10.1523/JNEUROSCI.23-26-08844.2003

10.1016/j.neuron.2005.10.028

10.3233/JAD-130560

10.1212/WNL.38.11.1688

10.1074/jbc.R109.080895

10.1097/00005072-199704000-00001

Dickson DW, 1988, Am J Pathol, 132, 86

10.1177/1073858407308518

10.1007/s00401-007-0284-8

10.1016/0197-4580(89)90131-0

10.1196/annals.1379.003

10.1007/s12035-014-8654-4

10.1038/ncomms13441

10.1523/JNEUROSCI.23-26-08967.2003

10.1002/(SICI)1097-4695(19990205)38:2<225::AID-NEU5>3.0.CO;2-H

10.3233/JAD-2007-11113

10.1007/s00401-013-1152-3

10.1113/EP085790

Kawai M, 1992, Am J Pathol, 140, 10.1016/j.ajpath.2015.11.025

10.1016/j.neuron.2008.06.008

10.1126/science.1169096

10.3389/fnins.2015.00469

10.1096/fj.01-0377com

10.1016/0896-6273(91)90170-5

Masliah E, 1993, Am J Pathol, 142

10.1523/JNEUROSCI.2650-04.2004

10.1038/nature06616

10.1016/j.neurobiolaging.2013.04.010

Miyawaki K, 2001, Acta Neuropathol, 102, 10.1007/s004010000354

Morris GP, 2014, Acta Neuropathol Commun, 2, 135

10.1002/bies.201400064

10.2174/156802606777323674

Ovsepian SV, 2017, Cereb Cortex, 27

10.1073/pnas.1017235108

10.1111/j.1460-9568.2007.05998.x

10.3233/JAD-150544

10.1016/j.jalz.2018.01.011

10.1038/nrn3504

10.1503/jpn.110190

Rifenburg RP, 1995, Neurodegeneration, 4

10.1007/s00401-016-1558-9

10.1523/JNEUROSCI.5274-12.2013

10.1002/ana.24125

10.1016/j.neuron.2014.10.024

10.1007/s004010050920

Vickers JC, 2016, Brain Res Bull, 126

10.2174/1567205013666151218150322

10.1046/j.1471-4159.1994.63031003.x

10.1007/s00424-009-0772-x

Thông tin
Thông tin xuất bản

Neuroscientist

Tập 25 Số 4

288-297

Thông tin tác giả