Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

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Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(2), P. 1436 - 1458

Published: Oct. 31, 2023

Plasma amyloid beta (Aβ) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need a comparative assessment to identify most valid future use in AD apply other settings which same may be useful, namely, cerebral angiopathy (CAA). CAA is progressive cerebrovascular characterized by deposition of Aβ

Language: Английский

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Core CSF Biomarker Profile in Cerebral Amyloid Angiopathy

Neurology, Journal Year: 2024, Volume and Issue: 103(7)

Published: Sept. 13, 2024

There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort improve diagnostics, especially the context patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA driver amyloid-related imaging abnormalities). We performed updated meta-analysis 5 core CSF (Aβ42, Aβ40, Aβ438, total tau [T-tau], phosphorylated [P-tau]) assess which these are most altered sporadic CAA.

Language: Английский

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Plasma Phosphorylated Tau 217 as a Discriminative Biomarker for Cerebral Amyloid Angiopathy

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(2)

Published: Feb. 1, 2025

ABSTRACT Background Blood‐based biomarkers may offer a non‐invasive approach to diagnose cerebral amyloid angiopathy (CAA), especially in early‐stage. We evaluated the ability of plasma phosphorylated tau‐217 (p‐tau 217) differentiate CAA from Alzheimer's disease (AD) and deep perforator arteriopathy (DPA). Methods Patients with AD (age 73.7 ± 8.1 years), probable (74.8 6.9 or DPA (66.1 10.4 years) were enrolled memory stroke clinics at medical center Taiwan. All participants received tau PET scans. Plasma measured via SIMOA immunoassay platform. The diagnostic utility p‐tau 217 was assessed using ROC analyses Youden cutoff. Associations between neuroimaging variables explored. Results had lower (0.69 0.76 vs. 1.28 0.97 pg/mL, p < 0.001) 217/Aβ40 ratio (0.003 0.002 0.006 0.003, than group but higher levels 217, 0.27 0.13 = 0.001; 217/Aβ40, 0.001 0.0005, 0.001), although adjustment attenuated difference DPA. Aβ40, Aβ42, Aβ40/Aβ42 not significantly different groups. moderate good (sensitivity, 64.4%; specificity, 89.5%; AUC, 0.809) 67.8%; 100%; 0.855). In CAA, correlated severity signal intensity, lobar microbleed count ( 0.001). Conclusions represent biomarker for distinguishing (CAA) other conditions, including

Language: Английский

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Circulating proteomic biomarkers for cerebral amyloid angiopathy screening and risk stratification

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

We systematically characterized plasma protein profiles in cerebral amyloid angiopathy (CAA) using proteomics and identified a hub panel for disease diagnosis risk stratification. A total of 146 patients with probable CAA 128 community-dwelling controls were prospectively enrolled. Plasma samples underwent proteomic analysis, the proteins validated two validation cohorts. Machine learning algorithms applied to construct validate performance circulating panel. 166 differentially expressed CAA. Six selected form panel, demonstrating excellent distinguish from all Additionally, stratification system derived accurately at high new-onset lobar intracerebral hemorrhage. Our findings revealed distinctive signatures established aiding screening proteomics. was developed validated, accuracy screening. The effectively stratified according future offers potential

Language: Английский

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Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta‐amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ 42/40 , phosphorylated‐tau (p‐tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) differ CAA their potential discriminate Boston Criteria 2.0 probable from healthy controls. METHODS Plasma p‐tau‐181, NfL, GFAP were quantified using single molecule array (Simoa) was also independently immunoprecipitation liquid chromatography mass‐spectrometry (IPMS). RESULTS Forty‐five participants with 47 controls had available plasma. ratios significantly lower than While p‐tau‐181 NfL elevated CAA, similar. A combination (Simoa), resulted an area under curve 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION those together can Highlights Participants reduced compared concentrations are similar Together, excellent discriminability for CAA.

Language: Английский

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The Spectrum of Cerebral Small Vessel Disease

Neurologic Clinics, Journal Year: 2024, Volume and Issue: 42(3), P. 663 - 688

Published: May 4, 2024

Language: Английский

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Fluid biomarkers in cerebral amyloid angiopathy

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 26, 2024

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation within leptomeninges and small/medium-sized cerebral blood vessels. Typically, haemorrhages are one first clinical manifestations CAA, posing considerable challenge to timely diagnosis CAA as bleedings only occur during later disease stages. Fluid biomarkers may change prior imaging biomarkers, therefore, they could be future diagnosis. Additionally, can used primary outcome markers in prospective trials. Among fluid blood-based offer distinct advantage over cerebrospinal do not require procedure invasive lumbar puncture. This article aimed provide an overview present data concerning associated with point out direction studies. all discussed, β, neurofilament light chain, matrix metalloproteinases, complement 3, uric acid, lactadherin demonstrated most promising evidence. However, field for under-researched area, cases, there or two studies on each mentioned this review. small sample size common limitation discussed Hence, it hard reach solid conclusion significance biomarker at different stages various subpopulations CAA. In order overcome issue, larger longitudinal multicentered needed.

Language: Английский

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Beta-Amyloid related neurodegenerative and neurovascular diseases: potential implications for transfusion medicine

Transfusion Medicine Reviews, Journal Year: 2024, Volume and Issue: 38(4), P. 150858 - 150858

Published: Sept. 18, 2024

Language: Английский

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Analysis of Speech Features in Alzheimer’s Disease with Machine Learning: A Case-Control Study

Healthcare, Journal Year: 2024, Volume and Issue: 12(21), P. 2194 - 2194

Published: Nov. 4, 2024

Background: Changes in the speech and language of patients with Alzheimer’s disease (AD) have been reported. Using machine learning to characterize these irregularities may contribute early, non-invasive diagnosis AD. Methods: We conducted cognitive function assessments, including Mini-Mental State Examination, 83 AD 75 healthy elderly participants, recorded pre- post-assessment conversations evaluate participants’ speech. analyzed characteristics spectrum, intensity, fundamental frequency, minute temporal variation (∆) intensity frequency compared them between participants. Additionally, we evaluated performance features that differed two groups as single explanatory variables. Results: found significant differences almost all elements spectrum groups. Regarding factors except for standard deviation In evaluation, areas under curve revealed by logistic regression analysis were higher center gravity (0.908 ± 0.036), mean skewness (0.904 0.023), kurtosis (0.932 (0.977 0.012) spectra. Conclusions: This study used reveal diagnosed comparison people. Significant components paving way early future.

Language: Английский

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