Inflammatory biomarkers in Alzheimer's disease plasma

Morgan, Angharad R.; Touchard, Samuel; Leckey, Claire; O’Hagan, Caroline; Nevado‐Holgado, Alejo J.; Barkhof, Frederik; Bertram, Lars; Blin, Olivier; Bos, Isabelle; Dobričić, Valerija; Engelborghs, Sebastiaan; Frisoni, Giovanni B.; Frölich, Lutz; Gabel, Silvey; Johannsen, Peter; Kettunen, Petronella; Kłoszewska, Iwona; Legido‐Quigley, Cristina; Lleó, Alberto; Martínez-Lage, Pablo; Mecocci, Patrizia; Meersmans, Karen; Molinuevo, José Luís; Peyratout, Gwendoline; Popp, Julius; Richardson, Jill C.; Sala, Isabel; Scheltens, Philip; Streffer, Johannes; Soininen, Hikka; Tainta, Mikel; Teunissen, Charlotte E.; Tsolaki, Magda; Vandenberghe, Rik; Visser, Pieter Jelle; Vos, Stephanie J.B.; Wahlund, Lars‐Olof; Wallin, Anders; Westwood, Sarah; Zetterberg, Henrik; Lovestone, Simon; Morgan, B. Paul; Disease, Alzheimer’s

doi:10.1016/j.jalz.2019.03.007

Cited by 153 publications

(126 citation statements)

References 52 publications

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“…Additionally, CD57 that prevents MAC assembly is decreased in AD brain (181). CSF and plasma levels of certain complement proteins have been reported as promising biomarkers for AD diagnosis and progression (182)(183)(184)(185)(186). These observations suggest that activation of the complement system may contribute to the AD pathogenesis.…”

Section: Role Of Complement In Alzheimer's Disease Brainmentioning

confidence: 99%

TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease

2020

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Amyloid plaques, mainly composed of abnormally aggregated amyloid β-protein (Aβ) in the brain parenchyma, and neurofibrillary tangles (NFTs), consisting of hyperphosphorylated tau protein aggregates in neurons, are two pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils and tau aggregates in the brain are closely associated with neuroinflammation and synapse loss, characterized by activated microglia and dystrophic neurites. Genome-wide genetic association studies revealed important roles of innate immune cells in the pathogenesis of late-onset AD by recognizing a dozen genetic risk loci that modulate innate immune activities. Furthermore, microglia, brain resident innate immune cells, have been increasingly recognized to play key, opposing roles in AD pathogenesis by either eliminating toxic Aβ aggregates and enhancing neuronal plasticity or producing proinflammatory cytokines, reactive oxygen species, and synaptotoxicity. Aggregated Aβ binds to toll-like receptor 4 (TLR4) and activates microglia, resulting in increased phagocytosis and cytokine production. Complement components are associated with amyloid plaques and NFTs. Aggregated Aβ can activate complement, leading to synapse pruning and loss by microglial phagocytosis. Systemic inflammation can activate microglial TLR4, NLRP3 inflammasome, and complement in the brain, leading to neuroinflammation, Aβ accumulation, synapse loss and neurodegeneration. The host immune response has been shown to function through complex crosstalk between the TLR, complement and inflammasome signaling pathways. Accordingly, targeting the molecular mechanisms underlying the TLR-complement-NLRP3 inflammasome signaling pathways can be a preventive and therapeutic approach for AD.

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Section: Role Of Complement In Alzheimer's Disease Brainmentioning

confidence: 99%

TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease

2020

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“…AD is a multifactorial disease that develops gradually with symptoms progressing with time, reflecting the need for early intervention [87]. In this regard, exploring biomarkers in AD that can predict the disease and monitor its progression while providing insight into the outcome of therapy are needed.…”

Section: Hmgb1 Rage and Tlr4 As Potential Clinical Biomarkers Of Admentioning

confidence: 99%

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Paudel

Angelopoulou

Piperi

et al. 2020

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Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.

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“…Recent studies demonstrate that this early diseaseaggravating central nervous system (CNS) inflammation starts decades before the appearance of severe cognitive decay or AD (18)(19)(20). Along this line, different longitudinal studies show that inflammation and microglial activation occur years before AD onset (21)(22)(23). Furthermore, there is a strong link between neuroinflammation and amyloid and tau accumulation in the human brain (23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

et al. 2020

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Inflammatory biomarkers in Alzheimer's disease plasma

Cited by 153 publications

References 52 publications

TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease

TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

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