Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102481 - 102481

Published: Sept. 3, 2024

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.

Language: Английский

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The Bio‐Hermes Study: Biomarker database developed to investigate blood‐based and digital biomarkers in community‐based, diverse populations clinically screened for Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2752 - 2765

Published: Feb. 28, 2024

Abstract INTRODUCTION Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many not positive. Use of blood‐based biomarkers may reduce screen failures. METHODS We recruited 755 non‐Hispanic White, 115 Hispanic, 112 Black, and 19 other minority across groups cognitively normal ( n = 417), mild cognitive impairment 312), or AD 272) participants. Plasma beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau, phosphorylated tau (p‐tau)181, p‐tau217 were measured; PET/CSF 956) determined positivity. Clinical, blood biomarker, ethnicity/race differences associated with status evaluated. RESULTS Greater impairment, older age, carrying an apolipoprotein E (apoE) ε4 allele greater burden. Areas under the receiver operating characteristic curve plasma p‐tau181, positivity ≥ 0.7117 all ethnoracial (p‐tau217, ≥0.8128). Age apoE adjustments imputation biomarker values outside limit quantitation provided small improvement in predictive power. DISCUSSION Blood‐based highly results diverse populations enrolled at clinical sites. Highlights Amyloid (Aβ)42/Aβ40, p‐tau 217 predicted P‐tau was strongest predictor Biomarkers from ethnic, racial, cohorts Community‐based have similar levels populations. A prescreen process assays number

Language: Английский

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Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease

Neuroscience, Journal Year: 2025, Volume and Issue: 567, P. 235 - 248

Published: Jan. 5, 2025

Language: Английский

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Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer's disease pathology: Review and recommendations

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 211, P. 111787 - 111787

Published: Feb. 1, 2023

Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests the gut microbiome (GM) plays pivotal role in pathogenesis AD through microbiota-gut-brain axis (MGB). Alterations GM composition and diversity have been observed both animal models human patients with AD. dysbiosis has implicated increased intestinal permeability, blood-brain barrier (BBB) impairment, neuroinflammation development hallmarks Further elucidation could pave way for holistic predictive methods determining risk progression disease. Furthermore, accumulating modulation alleviate adverse symptoms or serve as preventive measure. In addition, increasing shows Type 2 Diabetes Mellitus (T2DM) often comorbid AD, common alterations inflammatory response, which chart GM-related treatment interventions diseases. We conclude by exploring therapeutic potential alleviating reducing risk. we also propose future directions research, namely fecal microbiota transplantation (FMT) precision medicine.

Language: Английский

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Sensitive label-free detection of the biomarker phosphorylated tau−217 protein in Alzheimer's disease using a graphene-based solution-gated field effect transistor

Biosensors and Bioelectronics, Journal Year: 2023, Volume and Issue: 228, P. 115174 - 115174

Published: March 12, 2023

Language: Английский

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Amyloid-β and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer’s Disease

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Alzheimer's disease (AD) is a age-related neurodegenerative and major public health concern both in Texas, US Worldwide. This mainly characterized by amyloid-beta (Aβ) phosphorylated Tau (p-Tau) accumulation the brains of patients with AD increasing evidence suggests that these are key biomarkers AD. Both Aβ p-tau can be detected through various imaging techniques (such as positron emission tomography, PET) cerebrospinal fluid (CSF) analysis. The presence individuals, who asymptomatic or have mild cognitive impairment indicate an increased risk developing future. Furthermore, combination often used for more accurate diagnosis prediction progression. Along being disease, it associated other chronic conditions such cardiovascular obesity, depression, diabetes because studies shown comorbid make people vulnerable to In first part this review, we discuss biofluid-based Aβ, p-Tau & plasma could alternative sensitive technique diagnose second part, underlying molecular mechanisms linked how they affect clinical care.

Language: Английский

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Targeted drug delivery in neurodegenerative diseases: the role of nanotechnology

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 29, 2025

Neurodegenerative diseases, characterized by progressive neuronal loss and cognitive impairments, pose a significant global health challenge. This study explores the potential of nanotherapeutics as promising approach to enhance drug delivery across physiological barriers, particularly blood–brain barrier (BBB) blood-cerebrospinal fluid (B-CSFB). By employing nanoparticles, this research aims address critical challenges in diagnosis treatment conditions such Alzheimer’s, Parkinson’s, Huntington’s diseases. The multifactorial nature these disorders necessitates innovative solutions that leverage nanomedicine improve solubility, circulation time, targeted while minimizing off-target effects. findings underscore importance advancing applications develop effective therapeutic strategies can alleviate burden neurodegenerative diseases on individuals healthcare systems.

Language: Английский

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Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1700 - 1700

Published: June 23, 2023

Every cell biological textbook teaches us that the main role of plasma membrane is to separate cells from their neighborhood allow for a controlled composition intracellular space. The mostly hydrophobic nature presents an impenetrable barrier most hydrophilic molecules larger than 1 kDa. On other hand, cell-penetrating peptides (CPPs) are capable traversing this without compromising integrity, and they can do so on own or coupled cargos. Coupling biologically medically relevant cargos CPPs holds great promise delivering membrane-impermeable drugs into cells. If cargo able interact with certain types, uptake CPP–drug complex be tailored cell-type-specific. Besides outlining major penetration pathways CPPs, review aimed at deciphering how properties influence mechanisms CPPs. By summarizing extensive body experimental evidence, we argue more ordered, less flexible structure, often present in very diseases planned treated decreases cellular uptake. These correlations not only understanding biology but also rationally improving value translational clinical applications.

Language: Английский

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Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders

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

Published: Oct. 25, 2024

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.

Language: Английский

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A Multi-Label Deep Learning Model for Detailed Classification of Alzheimer's Disease

Actas Españolas de Psiquiatría, Journal Year: 2025, Volume and Issue: 53(1), P. 89 - 99

Published: Jan. 5, 2025

Background: Accurate diagnosis and classification of Alzheimer's disease (AD) are crucial for effective treatment management. Traditional diagnostic models, largely based on binary systems, fail to adequately capture the complexities variations across different stages subtypes AD, limiting their clinical utility. Methods: We developed a deep learning model integrating dot-product attention mechanism an innovative labeling system enhance AD severity levels. This processed various demographic data, emphasizing most relevant features diagnosis. The approach emphasized precision in identifying predicting through advanced computational techniques that mimic expert decision-making. Results: Comparative tests against baseline fully connected neural network demonstrated our proposed significantly improved accuracy. Our achieved accuracy 83.1% subtypes, compared 72.9% by baseline. In prediction, reached 83.3%, outperforming (73.5%). Conclusions: incorporation tailored enhances diagnosing classifying AD. improvement highlights potential support personalized strategies advance medicine neurodegenerative diseases.

Language: Английский

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