Progress of Chinese Medicine in Regulating Microglial Polarization against Alzheimer’s Disease DOI

Fengge Yang,

Wei Gao,

J Z Wang

и другие.

The American Journal of Chinese Medicine, Год журнала: 2024, Номер unknown, С. 1 - 21

Опубликована: Дек. 24, 2024

Alzheimer’s disease (AD), the predominant form of dementia, is a neurodegenerative disorder central nervous system (CNS) characterized by subtle onset and spectrum cognitive functional declines. The clinical manifestation AD encompasses memory deficits, deterioration, behavioral disturbances, culminating in severe impairment daily living skills. Despite its high prevalence, accounting for 60–70% all dementia cases, there remains an absence curative therapeutics. Microglia (MG), resident immune cells CNS, exhibit bifurcated role pathogenesis. Functioning neuroprotective capacity, MGs express scavenger receptors, facilitating clearance [Formula: see text]-amyloid protein (A[Formula: text]) cellular debris. Conversely, aberrant activation can lead to secretion pro-inflammatory cytokines, thereby propagating neuroinflammatory responses that are detrimental neuronal integrity. dynamics MG ensuing neuroinflammation pivotal evolution AD. Chinese medicine (CM), treasure trove traditional cultural practices, has demonstrated significant potential therapeutic management Over past triennium, CM garnered considerable research attention multifaceted approaches AD, including regulation polarization. This review synthesizes current knowledge on origins, polarization dynamics, mechanistic interplay with pathology. It further explores nexus between cardinal pathological hallmarks such as A[Formula: text] plaque deposition, hyperphosphorylation tau, synaptic plasticity impairments, neuroinflammation, brain–gut-axis dysregulation. also encapsulates strategies CM, which encompass monomers, formulae, acupuncture. These modulate context treatment, providing robust theoretical framework conduct future investigative endeavors both preclinical realms.

Язык: Английский

Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms DOI
Steven M. Greenberg, Francesco Bax, Susanne J. van Veluw

и другие.

Nature Reviews Neurology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Язык: Английский

Процитировано

9
Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer’s disease, and late-onset Alzheimer’s disease DOI Creative Commons
Mitchell Martà-Ariza, Dominique Leitner, Evgeny Kanshin

и другие.

Acta Neuropathologica, Год журнала: 2025, Номер 149(1)

Опубликована: Янв. 18, 2025

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar early-onset (EOAD) late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.99 y/o), EOAD (63 4.07 (82.1 6.37 controls (66.4 13.04). identified differentially abundant proteins when comparing plaques neighboring non-plaque tissue (FDR < 5%, fold-change > 1.5) in 132), 192), 128), 43 plaque-associated shared across all groups. Positive correlations were observed between (R2 .77), .73), .67). Top gene ontology biological processes (GOBP) included lysosomal transport (p 1.29 × 10−5) for immune system regulation 4.33 lysosome organization 0.029) LOAD. Protein networks revealed a protein signature involving metabolism, response, functions. In vs. control tissue, we 263, 269, 301 proteins, 65 altered cohorts. Non-plaque showed modest .59) .33) compared correlation .79). GOBP term groups was chromatin remodeling 0.001), additional terms including extracellular matrix, protein–DNA complexes expression Our study reveals key functional characteristics amyloid LOAD, highlighting pathways endo/lysosomal functions responses. The distinct alterations ECM structure, underscoring unique differences subtypes. findings enhance our understanding pathogenesis identify potential biomarkers therapeutic targets.

Язык: Английский

Процитировано

2
The Impact of Anti-Amyloid Immunotherapies on Stroke Care DOI Open Access
Philippe‐Antoine Bilodeau, John Dickson, Mariel G. Kozberg

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(5), С. 1245 - 1245

Опубликована: Фев. 22, 2024

Anti-amyloid immunotherapies have recently emerged as treatments for Alzheimer's disease. While these therapies demonstrated efficacy in clearing amyloid-β and slowing cognitive decline, they also been associated with amyloid-related imaging abnormalities (ARIA) which include both edema (ARIA-E) hemorrhage (ARIA-H). Given that ARIA significant morbidity cases of antithrombotic or thrombolytic therapy, an understanding mechanisms risk factors is critical importance stroke care. We discuss the latest data regarding ARIA, including role underlying cerebral amyloid angiopathy, implications ischemic prevention management.

Язык: Английский

Процитировано

8
Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease DOI Creative Commons

Eunshil Lee,

Yongmin Chang

Cells, Год журнала: 2025, Номер 14(3), С. 168 - 168

Опубликована: Янв. 22, 2025

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression

Язык: Английский

Процитировано

1
Synapse vulnerability and resilience underlying Alzheimer’s disease DOI Creative Commons
Raquel N. Taddei, Karen Duff

EBioMedicine, Год журнала: 2025, Номер 112, С. 105557 - 105557

Опубликована: Янв. 31, 2025

Synapse preservation is key for healthy cognitive ageing, and synapse loss represents a critical anatomical basis of dysfunction in Alzheimer's disease (AD), predicting dementia onset, severity, progression. viewed as primary pathologic event, preceding neuronal brain atrophy AD. Synapses may, therefore, represent one the earliest clinically most meaningful targets neuropathologic processes driving AD dementia. The highly selective particularly vulnerable synapses while leaving others, termed resilient, largely unaffected. Yet, anatomic molecular hallmarks resilient populations their association with changes (e.g. amyloid-β plaques tau tangles) memory remain poorly understood. Characterising selectively may be to understanding mechanisms versus enable development robust biomarkers disease-modifying therapies

Язык: Английский

Процитировано

1
Amyloid-Related Imaging Abnormalities in Clinical Trials of Gantenerumab in Early Alzheimer Disease DOI Creative Commons
Stephen Salloway, Jakub Wojtowicz,

Nicola Voyle

и другие.

JAMA Neurology, Год журнала: 2024, Номер 82(1), С. 19 - 19

Опубликована: Ноя. 18, 2024

Importance Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae. Objectives To describe the characteristics ARIA risk factors clinical consequences ARIA-edema (ARIA-E). Design, Setting, Participants Secondary data collection I/II randomized, double-blind, placebo-controlled, 116-week parallel-group extensions, PostGraduate, with up 210 (mean, 125) weeks total gantenerumab treatment were conducted between 2018 2023. The study included multicenter trials at 288 sites across 30 countries. enrolled 985 980 participants, respectively, early symptomatic Alzheimer disease (AD) amyloid-beta (Aβ) pathology who aged 50 90 years. PostGraduate 1382 participants (671 previously randomized gantenerumab). analyzed November 2, 2022, October 10, Interventions 1:1 or placebo. Nine-month uptitration was used mitigate risk. Main outcomes measures Postbaseline safety monitoring, brain magnetic resonance (MRI) findings, adverse events cognitive assessments. Results safety-evaluable MRI population comprised 1939 (mean age, 71.7 years; 1105 female [57.0%]). Severity AD–related Aβ neuropathology (lower cerebrospinal fluid [CSF] Aβ42, hazard ratio [HR] for CSF Aβ42: 0.4; 95% CI, 0.2-0.7) comorbid cerebrovascular (Fazekas score: HR, 1.6; 1.3-2.0; superficial siderosis count: 1.9; 1.3-2.6; microhemorrhage 1.3; 1.0-1.5) may be important baseline ARIA-E, in addition apolipoprotein E (APOE) ε4 status (APOE heterozygous carrier: 2.0; 1.4-2.8 APOE homozygous 4.7; 3.2-6.7). At group level, ARIA-E did not impact functional performance (relative difference adjusted means Clinical Dementia Rating–Sum Boxes −9% pooled analysis week 116 when censored first ARIA-E). While taking ARIA-hemosiderin occurred 24.9% (247 993) 22.9% (227 respectively; by 64 86.2% (213 247) ARIA-E. Narratives are provided all serious cases. Conclusions Relevance These results show that allele count, severity relevant clinicians prescribing anti-Aβ monoclonal antibodies AD developing individualized monitoring plans. Evaluation these other is recommended. Trial registrations ClinicalTrials.gov Identifiers: NCT03444870 , NCT03443973 NCT04374253 .

Язык: Английский

Процитировано

5
Astrocyte-neuron communication through the complement C3-C3aR pathway in Parkinson’s disease DOI Creative Commons

Xiaosa Chi,

Sijia Yin,

Yadi Sun

и другие.

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

4
Senescent microglia: The hidden culprits accelerating Alzheimer’s disease DOI
Li Wu,

Xie Yong-Yan,

Mu Jia-Xin

и другие.

Brain Research, Год журнала: 2025, Номер unknown, С. 149480 - 149480

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Altered Clearance and Amyloid-Related Imaging Abnormalities DOI
Petrice M. Cogswell, Brian J. Burkett, Derek R. Johnson

и другие.

Neuroimaging Clinics of North America, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Knowing the enemy: strategic targeting of complement to treat Alzheimer disease DOI
Andrea J. Tenner, Tiffany J. Petrisko

Nature Reviews Neurology, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

Процитировано

0