Amyloid‐Related Imaging Abnormality (ARIA) Beyond the APOE‐ε4 Allele DOI Creative Commons
Valentinus Besin, Farizky Martriano Humardani,

Fenny Yudiarto

et al.

Chronic Diseases and Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

ABSTRACT Monoclonal antibodies (mAbs) have made significant progress in the treatment of Alzheimer's disease (AD). However, mAbs are associated with adverse effects, including Amyloid‐Related Imaging Abnormality (ARIA), which manifests as edema or effusion (ARIA‐E) and hemorrhage (ARIA‐H). The mechanisms behind these effects not yet fully understood. Moreover, spontaneous ARIA has been insufficiently explored, mAb therapies, particularly lecanemab, mainly focused on patients APOE‐ε4 allele carrier. This review aims to address this gap by examining ARIA, induced mAbs, influence genetic variants development. autoantibody‐Aβ‐mediated immune response targets excessive Aβ deposits, increasing activity through microglial reactivity. heightened response, driven accumulation blood vessels, promotes angiopathy inflammation, potentially contributing ARIA. carrier is more strongly ARIA‐E because it redistributes deposition from brain influencing redistribution enhances vascular integrity reduces risk ARIA‐H. also increases likelihood due vasculature, triggering inflammation. In contrast, development ARIA‐H linked increased TREM2 expression reactivity, leading impaired disrupted matrix remodeling, worsens condition. Additionally, may extend beyond allele, possibly impacting other involved redistribution, integrity.

Language: Английский

Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? DOI Open Access
Poul Flemming Høilund‐Carlsen, Abass Alavi, Rudolph J. Castellani

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3892 - 3892

Published: March 31, 2024

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that protein amyloid-beta cause of disease. Two antibodies, aducanumab and lecanemab, have been approved by U.S. Food Drug Administration, while a third, donanemab, under review. main argument FDA approvals presumed therapy-induced removal cerebral deposits. Lecanemab donanemab are also thought to some statistical delay in determination cognitive decline. However, clinical efficacy less than with conventional treatment, selection amyloid-positive trial patients non-specific amyloid-PET imaging, uncertain amyloids trials cast doubt on this anti-Alzheimer's antibody therapy hence hypothesis, calling more thorough investigation negative impact type brain.

Language: Английский

Citations

14
Epigenetic Changes in Alzheimer’s Disease: DNA Methylation and Histone Modification DOI Creative Commons
Laura M. De Plano,

Alessandra Saitta,

Salvatore Oddo

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 719 - 719

Published: April 21, 2024

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss, imposing significant burden on affected individuals their families. Despite the recent promising progress in therapeutic approaches, more needs to be done understand intricate molecular mechanisms underlying development progression of AD. Growing evidence points epigenetic changes as playing pivotal role pathogenesis disease. The dynamic interplay between genetic environmental factors influences landscape AD, altering gene expression patterns associated with key pathological events pathogenesis. To this end, alterations not only impact genes implicated AD but also contribute dysregulation crucial cellular processes, including synaptic plasticity, neuroinflammation, oxidative stress. Understanding complex provides new avenues for interventions. This review comprehensively examines DNA methylation histone modifications context It aims deeper understanding facilitate targeted strategies.

Language: Английский

Citations

12
The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis DOI Creative Commons
Yiliang Liu,

Xuewen Xiao,

Yang Yang

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(7), P. 4841 - 4853

Published: June 11, 2024

The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood.

Language: Английский

Citations

11
Alzheimer’s Disease as Type 3 Diabetes: Understanding the Link and Implications DOI Open Access
Mateusz Kciuk, Weronika Kruczkowska, Julia Gałęziewska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11955 - 11955

Published: Nov. 7, 2024

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.

Language: Английский

Citations

11
Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer’s disease: a systematic review and network meta-analysis of randomized controlled trials DOI Creative Commons

Wenting Cai,

Hui Zhang,

Yan Wu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

Objective The aim of this study was to compare the efficacy and safety anti-tau protein monoclonal antibodies for Alzheimer’s disease (AD). Tau aggregation, a key pathological feature AD, is closely associated with neurodegeneration cognitive decline. Targeting tau has emerged as promising therapeutic strategy. By investigating effects on function, progression, overall quality life in patients which can provide valuable insights into their potential option devastating neurodegenerative disorder. Methods randomized controlled trials (RCTs) Gosuranemab, Semorinemab, Tilavonemab, Zagotenemab (AD) were systematically searched across PubMed, Embase, Web Science Cochrane Library, up May 2024. control group included placebo. indicators change Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum Boxes (CDR-SB), Disease Assessment Scale-Cognitive (ADAS-Cog), Cooperative Study-Activities Daily Living (ADCS-ADL) from baseline until time observation. Statistical analysis conducted using Stata 14 RevMan 5.4. purpose data processing, including generating network evidence plots, surface under cumulative ranking curve (SUCRA) ranking, league funnel visually summarize evaluate relative effectiveness publication bias multiple interventions. Mean differences (MD) 95% confidence interval (95%CI) effect sizes analyze continuous variables. Results This encompassed six RCTs involving 2,193 patients. Semorinemab more effective than placebo MMSE ADAS-Cog scores (MDs ranging between 0.52 3.21; MDs 0.17 3.30). Placebo showed relatively good according SUCRA CDR-SB ADCS-ADL (75.7 79.5%). Tilavonemab exhibited similar that two indicators. lower incidence AE, SAE, fall, urinary tract infections placebo, statistically significant. Most results no statistical difference. Conclusion indicated antibodies, such promise terms managing AD. Further studies are needed confirm these findings, assess long-term effects, refine treatment protocols. Systematic review registration https://www.crd.york.ac.uk/prospero/#myprospero , CRD42024583388.

Language: Английский

Citations

1
New implications for prion diseases therapy and prophylaxis DOI Creative Commons
Fangzhou Liu, Wenqi Lü, Ling Liu

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: March 4, 2024

Prion diseases are rare, fatal, progressive neurodegenerative disorders that affect both animal and human. Human prion mainly present as Creutzfeldt-Jakob disease (CJD). However, there no curable therapies, may negatively the ecosystem human society. Over past five decades, scientists devoting to finding available therapeutic or prophylactic agents for diseases. Numerous chemical compounds have been shown be effective in experimental research on diseases, but with limitations of toxicity, poor efficacy, low pharmacokinetics. The earliest clinical treatments CJD were almost carried out anti-infectious had little amelioration course. With discovery pathogenic misfolding protein (PrPSc) increasing insights into biology, amounts novel technologies attempted eliminate PrPSc. This review presents new perspectives including immunotherapy, gene therapy, small-molecule drug, stem cell therapy. It further explores prospects challenge associated these emerging approaches

Language: Английский

Citations

6
Biological markers of Alzheimer's disease in cerebrospinal fluid: clinical and laboratory comparisons DOI Creative Commons
K. V. Shevtsova, Д. О. Рожков, Д. А. Гришина

et al.

Neurology neuropsychiatry Psychosomatics, Journal Year: 2024, Volume and Issue: 16(3), P. 96 - 102

Published: June 22, 2024

Diagnostic hypothesis of Alzheimer's disease (AD) is based on the typical clinical picture and exclusion other diseases manifesting by cognitive behavioural disorders MRI scans brain laboratory tests. For an accurate diagnosis AD diseases, detection biological markers (biomarkers) in cerebrospinal fluid (CSF) great importance: a decrease level beta-amyloid (Ав^ -42) increase phosphorylated tau protein. The analysis biomarkers CSF 63 patients (16 men 47 women, mean age 72±8.7 years) with [30 moderate impairment (MCI) stage 33 mild dementia stage] allowed us to confirm 54 cases (85.3%) exclude it remaining nine (14.7%). We present case 59-year-old patient MCI whom were detected CSF, confirming AD. also observations two possible AD, results examination made rule out indicated hippocampal sclerosis tauopathy. At present, study practical importance, since at prevent progression anti-amyloid therapy. Currently, rarely diagnosed our country, so importance inform physicians about modern methods treatment

Language: Английский

Citations

6
Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs DOI Creative Commons
Yanxin Shen, Meng Zhao, Panpan Zhao

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 11, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be disease-modifying agent treatment AD. Lithium’s properties AD acting on multiple neuropathological targets, such reducing amyloid deposition tau phosphorylation, enhancing autophagy, neurogenesis, synaptic plasticity, regulating cholinergic glucose metabolism, inhibiting neuroinflammation, oxidative stress, apoptosis, while preserving mitochondrial function. Clinical trials demonstrated therapy can improve function patients with In particular, meta-analyses shown more safer than recently FDA-approved aducanumab improving The affordability therapeutic efficacy prompted reassessment its use. However, use lead to potential side effects safety issues, which limit clinical application. Currently, several new formulations are undergoing efficacy. This review focuses lithium’s mechanism action treating highlighting latest preclinical trials. It also explores coping strategies, offering strategy

Language: Английский

Citations

6
Alzheimer's disease: diagnosis and treatment, errors in patient management DOI Creative Commons
В. А. Парфенов, Д. А. Гришина,

A. Yu. Tyurina

et al.

Neurology neuropsychiatry Psychosomatics, Journal Year: 2024, Volume and Issue: 16(2), P. 95 - 100

Published: April 24, 2024

Alzheimer's disease (AD) is the most common degenerative of brain leading to dementia. AD cause disability among age-related diseases. The diagnosis based on clinical findings and confirmed by presence positive biological markers disease, which reflect pathological formation beta-amyloid tau protein in brain. Magnetic resonance imaging shows atrophy helps rule out other Psychosocial behavioral approaches form basis for treatment patients with AD; cognitive training combination regular physical exercise recommended. Acetylcholinesterase inhibitors glutamate receptor blocker memantine are used as drugs that improve functions AD. Dispersible forms treat dysphagia efficacy safety pathogenetic therapy aimed at eliminating cerebral passive immunization under discussion. Unfortunately, rarely diagnosed our country; doctors not sufficiently informed about modern methods Many observed misdiagnosis chronic cerebrovascular do receive effective therapy. A observation a patient early-onset presented, reflecting typical errors management. Issues optimizing management discussed.

Language: Английский

Citations

5
Advances in Aggrephagy: Mechanisms, Disease Implications, and Therapeutic Strategies DOI Open Access

Haixia Zhuang,

Xinyu Ma

Journal of Cellular Physiology, Journal Year: 2025, Volume and Issue: 240(1)

Published: Jan. 1, 2025

ABSTRACT The accumulation of misfolded proteins within cells leads to the formation protein aggregates that disrupt normal cellular functions and contribute a range human pathologies, notably neurodegenerative disorders. Consequently, investigation into mechanisms aggregate their subsequent clearance is considerable importance for development therapeutic strategies. predominantly achieved via autophagy‐lysosomal pathway, process known as aggrephagy. In this autophagosome biogenesis lysosomal digestion provide necessary conditions aggregates, while autophagy receptors such P62, NBR1, TAX1BP1, TOLLIP, CCT2 facilitate recognition by machinery, playing pivotal role in degradation. This review will introduce formation, progression, degradation, with particular emphasis on advances aggrephagy, providing insights aggregates‐related diseases novel

Language: Английский

Citations

0