Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain

Proceedings of the National Academy of Sciences of the United States of America
Lindsay A WelikovitchA C Cuello

Abstract

Chronic inflammation during Alzheimer's disease (AD) is most often attributed to sustained microglial activation in response to amyloid-β (Aβ) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neurons burdened with increasing levels of soluble and oligomeric Aβ, which are known to be the most toxic amyloid species within the brain. Laser microdissected neurons extracted from preplaque amyloid precursor protein (APP) transgenic rats were found to produce a variety of potent immune factors, both at the transcript and protein levels. Neuron-derived cytokines correlated with the extent of microglial activation and mobilization, even in the absence of extracellular plaques and cell death. Importantly, we identified an inflammatory profile unique to Aβ-burdened neurons, since neighboring glial cells did not express similar molecules. Moreover, we demonstrate within disease-vulnerable regions of the human brain that a neuron-specific in...Continue Reading

References

Jan 1, 1988·Acta Neuropathologica·P L McGeerE G McGeer
Jan 1, 1982·Acta Neuropathologica·P Eikelenboom, F C Stam
Nov 1, 1982·Journal of the Neurological Sciences·G K Wilcock, M M Esiri
Nov 1, 1994·The Tohoku Journal of Experimental Medicine·H Akiyama
Jan 7, 2000·The American Journal of Pathology·G K GourasN R Relkin
Apr 18, 2002·Neurobiology of Aging·Valerie A M VincentGreer M Murphy
Nov 5, 2002·The American Journal of Pathology·Reisuke H TakahashiGunnar K Gouras
May 17, 2005·Nature Neuroscience·Dimitrios DavalosWen-Biao Gan
Nov 26, 2005·Neurobiology of Aging·Daniela GalimbertiElio Scarpini
Apr 12, 2006·Archives of Neurology·Daniela GalimbertiElio Scarpini
May 12, 2006·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·E RotaP Ferrero
Jul 18, 2006·Journal of the Neurological Sciences·Michael RentzosDemetris Vassilopoulos D
Mar 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tomomi KiyotaTsuneya Ikezu
Apr 3, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hiroaki WakeJunichi Nabekura
Jul 25, 2009·Molecular Neurobiology·Marina A Lynch
Dec 15, 2010·Current Alzheimer Research·M T FerrettiA C Cuello
Mar 19, 2011·Neurobiology of Aging·Maria Teresa FerrettiA Claudio Cuello
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
Jul 26, 2011·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·John C BreitnerUNKNOWN ADAPT Research Group
Feb 18, 2012·The Cochrane Database of Systematic Reviews·Darin JaturapatpornNaji Tabet

❮ Previous
Next ❯

Citations

Nov 13, 2020·Clinical Microbiology Reviews·Anthony L KomaroffSteven Jacobson
Dec 18, 2020·Frontiers in Veterinary Science·Sonja Prpar MihevcGregor Majdič
Nov 19, 2020·Brain : a Journal of Neurology·Lisi Flores-AguilarA Claudio Cuello
Feb 17, 2021·Current Opinion in Neurology·Rupal I Mehta, Julie A Schneider
Mar 6, 2021·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Julie HoogmartensChristine Van Broeckhoven
Jul 31, 2020·Nano Today·Pengyu ChenChunying Chen
Jun 29, 2021·Journal of Alzheimer's Disease : JAD·Suman ChaudharyNeena Singh
Oct 18, 2021·Journal of Neurochemistry·Stephen D GinsbergGabriela Chiosis

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
laser-capture microdissection
Profiler
PCR
confocal microscopy

Software Mentioned

Stellaris Probe Designer
ImageJ
Zen

Related Concepts

Related Feeds

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Gunjan D ManochaColin K Combs
© 2021 Meta ULC. All rights reserved