Neuroinflammation in Alzheimer’s Disease DOI Creative Commons
Isaac G. Onyango, Gretsen Velezmoro Jáuregui, Mária Čarná

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 524 - 524

Published: May 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Language: Английский

Alzheimer's disease DOI
Philip Scheltens, Bart De Strooper, Miia Kivipelto

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10284), P. 1577 - 1590

Published: March 2, 2021

Language: Английский

Citations

3039
Microglia states and nomenclature: A field at its crossroads DOI Creative Commons
Rosa Chiara Paolicelli, Amanda Sierra, Beth Stevens

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3458 - 3483

Published: Nov. 1, 2022

Language: Английский

Citations

1043
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease DOI Creative Commons
Wei-Ting Chen,

Ashley Lu,

Katleen Craessaerts

et al.

Cell, Journal Year: 2020, Volume and Issue: 182(4), P. 976 - 991.e19

Published: July 22, 2020

Language: Английский

Citations

708
Alzheimer's disease DOI

José Arguedas López,

Hector M. González, Gabriel C. Léger

et al.

Handbook of clinical neurology, Journal Year: 2019, Volume and Issue: unknown, P. 231 - 255

Published: Jan. 1, 2019

Language: Английский

Citations

628
Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis DOI
Phuong H. Nguyen, Ayyalusamy Ramamoorthy, Bikash R. Sahoo

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(4), P. 2545 - 2647

Published: Feb. 5, 2021

Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural dynamic characterization all species along pathways from monomers to fibrils challenging by experimental computational means because they involve intrinsically disordered proteins most diseases. Yet understanding how amyloid become toxic challenge developing treatment for these Here we review what computer, vitro, vivo, pharmacological experiments tell us about accumulation deposition oligomers (Aβ, tau), α-synuclein, IAPP, superoxide dismutase 1 proteins, which have been mainstream concept underlying Alzheimer's disease (AD), Parkinson's (PD), type II diabetes (T2D), amyotrophic lateral sclerosis (ALS) research, respectively, years.

Language: Английский

Citations

539
Dysregulation of brain and choroid plexus cell types in severe COVID-19 DOI Creative Commons
Andrew C. Yang, Fabian Kern, Patricia Morán Losada

et al.

Nature, Journal Year: 2021, Volume and Issue: 595(7868), P. 565 - 571

Published: June 21, 2021

Language: Английский

Citations

527
TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge DOI Creative Commons

Alicia Nugent,

Karin Lin,

Bettina van Lengerich

et al.

Neuron, Journal Year: 2020, Volume and Issue: 105(5), P. 837 - 854.e9

Published: Jan. 2, 2020

Language: Английский

Citations

514
cGAS–STING drives ageing-related inflammation and neurodegeneration DOI Creative Commons
Muhammet F. Gülen,

Natasha Samson,

Alexander Keller

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7973), P. 374 - 380

Published: Aug. 2, 2023

Low-grade inflammation is a hallmark of old age and central driver ageing-associated impairment disease1. Multiple factors can contribute to inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling their impact in natural ageing remain unclear. Here we show cGAS-STING pathway, which mediates immune sensing DNA3, critical chronic functional decline during ageing. Blockade STING suppresses phenotypes senescent human cells tissues, attenuates ageing-related multiple peripheral organs brain mice, leads an improvement tissue function. Focusing on brain, reveal activation triggers reactive microglial transcriptional states, neurodegeneration cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity microglia, defining mechanism by engaged brain. Single-nucleus RNA-sequencing analysis microglia hippocampi gain-of-function mouse model demonstrates engagement sufficient direct states leading bystander cell inflammation, neurotoxicity impaired memory capacity. Our findings establish pathway as blockade potential strategy halt neurodegenerative processes age.

Language: Английский

Citations

414
Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model DOI Creative Commons
Shoutang Wang, Meer Mustafa, Carla M. Yuede

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(9)

Published: June 24, 2020

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models amyloid β (Aβ) accumulation, defective function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas overexpression attenuates pathology. Thus, AD may benefit from activation. Here, we examined the impact an anti-human agonistic mAb, AL002c, model expressing either common (CV) or TREM2. Single-cell RNA-seq microglia after acute systemic administration AL002c showed induction proliferation both CV- R47H-transgenic mice. Prolonged reduced filamentous plaques neurite dystrophy, impacted behavior, tempered inflammatory response. We further that safe well tolerated first-in-human phase I clinical trial engages based on cerebrospinal fluid biomarkers. conclude AL002 promising candidate therapy.

Language: Английский

Citations

370
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies DOI Creative Commons
Ana‐Caroline Raulin, Sydney V. Doss, Zachary A. Trottier

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Nov. 8, 2022

Alzheimer's disease (AD) is the most common cause of dementia worldwide, and its prevalence rapidly increasing due to extended lifespans. Among number genetic risk factors identified, apolipoprotein E (APOE) gene remains strongest prevalent, impacting more than half all AD cases. While ε4 allele APOE significantly increases risk, ε2 protective relative ε3 allele. These alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function mediate lipid transport in brain periphery; however, additional functions diverse biological have been recognized. Pathogenically, seeds amyloid-β (Aβ) plaques with apoE4 driving earlier abundant amyloids. ApoE also differential effects on multiple Aβ-related or Aβ-independent pathways. complexity biology pathobiology presents challenges designing effective apoE-targeted therapeutic strategies. This review examines key pathobiological pathways related targeting strategies a specific focus latest technological advances tools.

Language: Английский

Citations

326