A real-world safety surveillance study of aducanumab through the FDA adverse event reporting system DOI Creative Commons
Jingjing Huang,

Xiaohong Long,

Chunyong Chen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Background Alzheimer’s disease poses a major public health challenge, with aducanumab’s approval in 2021 as the first disease-modifying therapy raising important safety considerations. This study analyzed Food Drug Administration Adverse Event Reporting System (FAERS) database to evaluate real-world profile and identify potential risk factors. Methods We conducted comprehensive pharmacovigilance using FAERS from January 2004 June 2024, analyzing 510 aducanumab-associated reports integrated databases containing over 18 million demographic records 66 drug records. Safety signals were evaluated four complementary disproportionality methods: Odds Ratio (ROR), Proportional (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), Multi-item Gamma Poisson Shrinker (MGPS). Analyses stratified by age sex, adverse events examined at both Organ Class (SOC) Preferred Term (PT) levels SAS 9.4. Results Among event reports, predominantly elderly patients (55.49% aged ≥65 years), nervous system disorders most frequent (53.24%, n = 583). Amyloid related imaging abnormality-oedema/effusion (ARIA-E) abnormality-microhaemorrhages haemosiderin deposits (ARIA-H) emerged significant (ROR: 53,538.3 38,187.9, respectively). Sex-stratified analysis showed comparable profiles between males females, ARIA-E events, ARIA-H maintaining strong across all groups, particularly ≥75 years. The median time onset was 146.0 days (IQR: 80.0–195.0). Temporal revealed increasing signal strength for ARIA-related 2004–2024, notable intensification during 2022–2023. Conclusion Our identified primary concern aducanumab, typically occurring within 146 of treatment initiation, sex but heightened risks These findings support viability therapeutic option while emphasizing critical importance rigorous monitoring protocols, ARIA year treatment.

Language: Английский

Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways DOI Creative Commons
Oliwia Koszła, Przemysław Sołek

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 30, 2024

The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities neurodegenerative disease. Central to these disorders lies among other factors, aberrant folding, aggregation, and accumulation proteins, resulting formation toxic entities that contribute neuronal degeneration. This review concentrates on key proteins such as β-amyloid (Aβ), tau, α-synuclein, elucidating intricate molecular events underlying their misfolding aggregation. We critically evaluate mechanisms governing elimination misfolded shedding light potential strategies. specifically examine pathways endoplasmic reticulum (ER) unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), intersecting signaling Keap1-Nrf2-ARE, along with connected through p62. Above all, we emphasize significance quality control mechanisms, encompassing interventions targeting regulation post-translational modifications, enhancement chaperones clearance. Additionally, focus current new, multi-target approaches. In conclusion, this systematically consolidates insights into emerging strategies predicated aggregates

Language: Английский

Citations

20
The Common Alzheimer's Disease Research Ontology (CADRO) for biomarker categorization DOI Creative Commons
Amanda M. Leisgang Osse,

Jefferson W. Kinney,

Jeffrey L. Cummings

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Language: Английский

Citations

2
Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History DOI Open Access
Félix Bermejo‐Pareja,

Teodoro del Ser

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(2), P. 536 - 536

Published: Jan. 17, 2024

Background: The concept of Alzheimer disease (AD)—since its histological discovery by to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review this field with bibliography selection (giving preference Medline best match). Results: following subjects are reviewed and discussed: Alzheimer’s discovery, Kraepelin’s creation new that was rare condition until 1970′s, growing interest investment in AD as major killer society large elderly population second half 20th century, consolidation clinicopathological model, modern nosology based on dominant amyloid hypothesis among many others. In 21st development biomarkers has supported novel biological definition AD, although proposed therapies have failed cure disease. incidence dementia/AD shown decrease affluent countries (possibly due control risk factors), mixed dementia been established most frequent etiology oldest old. Conclusions: current lacks unanimity. Many hypotheses attempt explain complex physiopathology entwined aging, cascade yielded poor therapeutic results. reduction appears promising but it should be confirmed future. A reevaluation is also necessary.

Language: Английский

Citations

10
Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer’s disease DOI Creative Commons
Geetika Nehra, Bryan Maloney,

Rebecca Smith

et al.

Fluids and Barriers of the CNS, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 9, 2025

Blood–brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and recognized as both a cause consequence the pathological cascade leading to cognitive decline. The goal this study was assess markers for in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at time autopsy determine what extent these are associated neuropathologic changes (ADNC) impairment. We used brain plasma 19 participants: 9 CNI 10 dementia patients had come University Kentucky Research Center (UK-ADRC) community-based cohort; all cases confirmed severe ADNC. Plasma obtained within 2 years autopsy. Aβ40, Aβ42, tau levels quantified by ELISA. Cortical sections cleared using X-CLARITY™ system immunostained neurovascular unit-related proteins. Brain slices then imaged confocal microscopy analyzed microvascular diameters immunoreactivity coverage Fiji/ImageJ. Isolated human microvessels assayed tight-junction protein expression JESS™ automated Western blot system. S100 calcium-binding B (S100β), matrix metalloproteinase (MMP)-2, MMP-9, neuron-specific enolase (NSE) All outcomes assessed linear associations global function (MMSE, CDR) cerebral atrophy scores Pearson, polyserial, polychoric correlation, appropriate, along generalized modeling mixed-level modeling. As expected, we detected elevated Aβ pathology compared CNI. However, found no differences sections. also observed claudin-5 capillaries isolated samples. biomarker analysis showed that 12.4-fold higher S100β levels, twofold lower NSE 2.4-fold MMP-9 1.2-fold MMP-2 than Data revealed predictive Our data suggest among different relevant dysfunction, most promising diagnostic Further investigation necessary how relate whether they may predict clinical outcomes, particularly prodromal early stages AD.

Language: Английский

Citations

1
Postbiotics as a Therapeutic Tool in Alzheimer's Disease: Insights into Molecular Pathways and Neuroprotective Effects DOI

Garry Hunjan,

Khadga Raj Aran

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102685 - 102685

Published: Feb. 1, 2025

Language: Английский

Citations

1
Implicative role of cytokines in neuroinflammation mediated AD and associated signaling pathways: Current progress in molecular signaling and therapeutics DOI
Sneha Kumari,

Rishika Dhapola,

Prajjwal Sharma

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102098 - 102098

Published: Oct. 30, 2023

Language: Английский

Citations

17
Approved drugs and natural products at clinical stages for treating Alzheimer’s disease DOI

Yajing Ma,

Sufang Liu,

Qingfeng Zhou

et al.

Chinese Journal of Natural Medicines, Journal Year: 2024, Volume and Issue: 22(8), P. 699 - 710

Published: Aug. 1, 2024

Language: Английский

Citations

7
Intranasal liposomes co-delivery of Aβ-targeted KLVFF and ROS-responsive ceria for synergistic therapy of Alzheimer’s disease DOI Creative Commons

Qiujie Shan,

Yue Zhi,

Yi Chen

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 494, P. 153210 - 153210

Published: June 16, 2024

β-Amyloid (Aβ) aggregation and oxidative stress are primary pathological features of Alzheimer's disease (AD). Combination therapies that target brain tissue corporately address these main factors required for effective AD treatment. Here, we developed a multifunctional liposome delivery system (KLVFF@LIP-CeO2) co-delivery Aβ-targeted KLVFF reactive oxygen species (ROS)-responsive Ceria (CeO2) through intranasal administration. After Aβ1-42-induced ROS apoptosis in HT22 cells, KLVFF@LIP-CeO2 exhibited significant protective effects by inhibiting Aβ scavenging multi-ROS. With features, verified the therapeutic effectiveness APPswe/PSEN1dE9 (APP/PS1) model mice. administration, demonstrated sufficient rapid accumulation significantly alleviated deposition stress, contributing to rescue cognitive impairment APP/PS1 These results highlight clinical potential multi-targeted nanoparticles synergistic therapy AD.

Language: Английский

Citations

6
A multifunctional carbon quantum dot overcoming the BBB for modulating amyloid aggregation and scavenging reactive oxygen species DOI
Chaoren Yan,

Yixuan Wang,

Yandong Ma

et al.

Materials Today Chemistry, Journal Year: 2024, Volume and Issue: 40, P. 102222 - 102222

Published: July 24, 2024

Language: Английский

Citations

6
Biological and Physical Performance Markers for Early Detection of Cognitive Impairment in Older Adults DOI Open Access
Hanna Kerminen, Emanuele Marzetti, Emanuela D’Angelo

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(3), P. 806 - 806

Published: Jan. 30, 2024

Dementia is a major cause of poor quality life, disability, and mortality in old age. According to the geroscience paradigm, mechanisms that drive aging process are also involved pathogenesis chronic degenerative diseases, including dementia. The dissection such therefore instrumental providing biological targets for interventions new sources biomarkers. Within several biomarkers have been discovered can be measured blood allow early identification individuals at risk cognitive impairment. Examples markers include inflammatory biomolecules, neuroaxonal damage, extracellular vesicles, DNA methylation. Furthermore, gait speed, usual fast pace as part dual task, has shown detect future Here, we provide an overview available may used gauge impairment apparently healthy older adults. Further research should establish which combination possesses highest predictive accuracy toward incident implementation currently large share at-risk whom preventive implemented maintain or increase reserves, thereby reducing progression

Language: Английский

Citations

5