Comprehensive Overview of Alzheimer’s Disease: Etiological Insights and Degradation Strategies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6901 - 6901

Published: June 24, 2024

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD associated with cognitive decline memory loss that worsens aging. A statistical report using U.S. data on estimates approximately 6.9 million suffer from AD, a number projected to surge 13.8 by 2060. Thus, there critical imperative pinpoint address its hallmark tau protein aggregation early prevent manage debilitating effects. Amyloid-β proteins are primarily formation plaques neurofibril tangles in brain. Current research efforts focus degrading amyloid-β or inhibiting their synthesis, particularly targeting APP processing hyperphosphorylation, aiming develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies trials treatments truly make difference. Genome-wide association (GWASs) across various cohorts identified 40 loci over 300 genes AD. Despite wealth genetic data, much remains be understood about functions these role process, prompting continued investigation. By delving deeper into associations, novel targets such as kinases, proteases, cytokines, degradation pathways, offer new directions for drug discovery therapeutic intervention This review delves biological pathways disrupted identifies how variations within could serve potential treatment strategies. Through comprehensive understanding molecular underpinnings researchers aim pave way more therapies can alleviate burden devastating disease.

Language: Английский

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Early- and Late-Onset Alzheimer’s Disease: Two Sides of the Same Coin?

Diseases, Journal Year: 2024, Volume and Issue: 12(6), P. 110 - 110

Published: May 22, 2024

Early-onset Alzheimer’s disease (EOAD), defined as onset before 65 years of age, has been significantly less studied than the “classic” late-onset form (LOAD), although EOAD often presents with a more aggressive course, caused by variants in APP, PSEN1, and PSEN2 genes. significant differences from LOAD, including encompassing diverse phenotypic manifestations, increased genetic predisposition, variations neuropathological burden distribution. Phenotypically, can be manifested non-amnestic variants, sparing hippocampi tau burden. The aim this article is to review different bases, risk factors, pathological mechanisms, diagnostic approaches between LOAD suggest steps further our understanding. comprehension monogenic provide valuable insights that may serve roadmap for understanding common disease.

Language: Английский

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Analysis of the causal relationship between five chosen factors and early-onset Alzheimer's disease: A Mendelian randomization study

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Background This study aims to explore the causal relationship between five selected factors— lysosome, migrasomes, macrophage, fibroblast, and endothelium cell—and early-onset Alzheimer's disease (EOAD) through related genes, providing clues for EOAD research. Methods Using genes factors as exposure variables outcome, significant were screened Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) method, based on OpenGWAS database. The intersected with assess relationships EOAD. Results MR identified 13 in total. Six of these protective EOAD, LYST being most (OR = 0.4259, 95% CI: 0.2218–0.8178, p 0.0103). Seven risk NCF4 2.7207, 1.0229–7.2362, 0.0449). A total 1925 cell analyzed. After intersection, 10 lysosome-related (NCF4, VIPAS39, LYST, SORT1, ARSB, EPDR1, SYNGR1, ANXA11, PYGB, CLN5) 3 -related (ADM, NFIB, NKTR) found have Conclusions There are lysosome that while no provides an important basis further

Language: Английский

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Neurostimulation devices to treat Alzheimer’s disease

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The use of neurostimulation devices for the treatment Alzheimer’s disease (AD) is a growing field. In this review, we examine mechanism action and therapeutic indications these in AD process. Rapid advancements technologies are providing non-pharmacological relief to patients affected by pathology. Neurostimulation therapies include electrical stimulation that targets circuitry-level connection important brain areas such as hippocampus induce neuromodulation dysfunctional neural circuitry electromagnetic field (EMF) anti-amyloid molecular pathways promote degradation beta-amyloid (Aβ). These target specific or diffuse cortical subcortical modulate neuronal activity at electrophysiological pathway level, effects AD. This review attempts determine most effective safe device provides an overview potential current clinical indications. Several EMF have shown beneficial harmful effect cell cultures animal models but not human studies. contradictory results may be related parameters devices, frequency, penetration depth, power deposition measured absorption rate, time exposure, type cell, tissue dielectric properties. Based on this, determining optimal understanding their essential application, our suggests repeated (REMFS) appropriate treatments. Before its it necessary consider complicated interconnected genetic epigenetic REMFS-biological system interaction. will move forward urgently needed therapy

Language: Английский

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Krüppel‐like factor 4 transcription factor in blood–brain barrier endothelial cells: A potential role in Alzheimer's disease

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide, with no sufficient cure. Ongoing research focused on developing new therapies aimed at preventing or delaying onset of symptoms, slowing progression, and improving cognitive behavioral outcomes in individuals affected by disease. Among various pathological changes associated this condition, blood-brain barrier (BBB) leakage plays a crucial role as it serves vital boundary for maintaining central nervous system (CNS) health. Preserving integrity functionality BBB essential to protect brain from amyloid-β accumulation, neuroinflammation, neuronal degeneration. This review summarizes models characterized over time. More importantly, we introduce Krüppel-like factor 4 (KLF4), transcription involved vascular systems, discuss its relevance By elucidating functions KLF4 within both CNSs, highlights potential modulating pathology, which may contribute therapeutic strategies managing debilitating condition.

Language: Английский

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Biomaterial-Based Additive Manufactured Composite Scaffolds for Tissue Engineering and Regenerative Medicine: A Comprehensive Review

Polymers, Journal Year: 2025, Volume and Issue: 17(8), P. 1090 - 1090

Published: April 17, 2025

Additive manufacturing (AM), also referred to as three-dimensional printing/printed (3DP), has emerged a transformative approach in the current design and of various biomaterials for restoration damaged tissues inside body. This advancement greatly aided development customized biomedical devices including implants, prosthetics, orthotics that are specific patients. In tissue engineering (TE), AM enables fabrication complex structures promote desirable cellular responses regeneration tissues. Since choice plays vital role scaffold performance well responses, meticulous material selection is essential optimizing functionality scaffolds. These scaffolds often possess certain characteristics such biodegradability, biocompatibility, biomimicry, porous structure. To this end, polymers chitosan, collagen, alginate, hyaluronic acid, polyglycolic polylactic polycaprolactone have been extensively investigated tissue-engineered Furthermore, combinations utilized further enhance scaffolds’ functionality. review discusses principle explores recent advancements technologies TE regenerative medicine. addition, applications 3DP, polymer-based will be highlighted.

Language: Английский

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Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11272 - 11272

Published: Oct. 19, 2024

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through microbiota–gut–brain axis, including Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis recent findings on involvement neuroinflammatory processes associated with AD, emphasizing novel insights therapeutic implications. reveals that dysbiosis AD patients’ is linked heightened peripheral central inflammatory responses. Specific bacterial taxa, such as Bacteroides Firmicutes gut, well Porphyromonas gingivalis cavity, are notably altered leading significant changes microglial activation cytokine production. Gut alterations increased intestinal permeability, facilitating translocation endotoxins like lipopolysaccharides (LPS) into bloodstream exacerbating by activating brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, short-chain fatty acids (SCFAs) amyloid peptides, can cross blood-brain barrier modulate While microbial amyloids may contribute amyloid-beta aggregation brain, certain SCFAs butyrate exhibit anti-inflammatory properties, suggesting potential avenue mitigate neuroinflammation. not only highlights critical pathology but also offers ray hope modulating could represent strategy for reducing slowing progression.

Language: Английский

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Global Initiatives and Collaborations in AI for Alzheimer's Disease

Advances in medical technologies and clinical practice book series, Journal Year: 2024, Volume and Issue: unknown, P. 342 - 355

Published: June 28, 2024

This summary discusses the significance of global initiatives and collaborations in field artificial intelligence (AI) for prognosis remedy Alzheimer's ailment. disease is a debilitating neurodegenerative ailment that affects tens millions people worldwide, its incidence expected to growth with aging populace. AI has emerged as promising tool early detection, correct prognosis, customized treatment disorder. However, fully harness capacity AI, interdisciplinary worldwide projects are critical. abstract sheds mild on modern nation studies sickness, highlighting important thing demanding situations opportunities collaborations. It additionally information sharing open technological know-how advancing emphasizes want moral considerations inside development deployment technologies.

Language: Английский

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The aged female rhesus macaque as a translational model for human menopause and hormone therapy

Hormones and Behavior, Journal Year: 2024, Volume and Issue: 166, P. 105658 - 105658

Published: Nov. 1, 2024

Language: Английский

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Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract Alzheimer’s Disease (AD) is characterized by its complex and heterogeneous etiology gradual progression, leading to high drug failure rates in late-stage clinical trials. In order better stratify individuals at risk for AD discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks polygenic scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, evaluated correlations the with previously defined on basis domain-specific cognitive functioning neuroimaging biomarkers. Employing PageRank algorithm, identified priority subtypes. Pathway analysis genes demonstrated associations neurodegeneration suggested candidate drugs currently utilized diabetes, hypertension, epilepsy repositioning AD. Experimental validation human induced pluripotent stem cell (hiPSC)-derived astrocytes modifying effects estradiol, levetiracetam, pioglitazone expression APOE complement C4 genes, suggesting

Language: Английский

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