Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6542 - 6555

Published: Aug. 6, 2024

Abstract BACKGROUND Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that occurs during the SCD stage, aiming discover biomarkers SCD. METHODS Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 654) and Disease Neuroimaging Initiative (ADNI, 650), representing different ethnicities stages, were included assess function using diffusion tensor image analysis along perivascular space (DTI‐ALPS). RESULTS Abnormal with ALPS index demonstrating excellent classification performance normal controls (area under receiver operating curve [AUC] SILCODE 0.816, AUC ADNI 0.797). Lower indicates higher progression, which negatively correlated Questionnaire 9 scores amyloid positron emission tomography burden. DISSCUSION Our study suggests serve biomarker Highlights Glymphatic characterized by (ALPS) becomes abnormal in subjective (SCD), earliest symptomatic manifestation preclinical (AD). The demonstrates East Asian Western cohorts. lower show clinical progression. closely associated serval scales beta

Language: Английский

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Present and Future of Blood-Based Biomarkers of Alzheimer’s Disease: Beyond the Classics

Brain Research, Journal Year: 2024, Volume and Issue: 1830, P. 148812 - 148812

Published: Feb. 17, 2024

Language: Английский

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Enzyme-responsive, multi-lock optical probes for molecular imaging and disease theranostics

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Enzyme-responsive, multi-lock optical probes exhibit superior detection specificity towards certain biomolecular events and pathological conditions, offering high disease diagnostic accuracy treatment efficacy.

Language: Английский

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Manual acupuncture benignly regulates blood-brain barrier disruption and reduces lipopolysaccharide loading and systemic inflammation, possibly by adjusting the gut microbiota

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Oct. 13, 2022

Background Blood-brain barrier (BBB) disruption and gut microbiota dysbiosis play crucial roles in Alzheimer’s disease (AD). Lipopolysaccharide (LPS) stimulation triggered by microbial is an important factor BBB systemic inflammation, but the mechanism of acupuncture regulation via AD not clear. Objective The current study evaluated effect manual (MA) on dysfunction APP/PS1 mice examined AD. Methods Acupoints were applied to Baihui (GV20), Yintang (GV29), Zusanli (ST36) MA group. Mice plus antibiotics (MAa) group received acupuncture, while probiotics (P) probiotics. Alterations spatial learning memory, microbiota, tightly connected structure permeability BBB, expression LPS inflammatory factors each assessed. Results Compared normal (N) group, cognitive ability was significantly impaired, composition markedly altered, disrupted, serum brain, TNF-α, IL-1β increased ( p < 0.01). These changes inhibited P groups 0.01 or 0.05), reversed benign regulatory effects 0.05). Conclusion Manual benignly modulated dysfunction, reduced LPS, IL-1β. comparable decrease load inflammation may be a potential target for acupuncture.

Language: Английский

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Small-molecule theranostics in Alzheimer's disease

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 255, P. 115382 - 115382

Published: April 22, 2023

Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed countries, due to rising life expectancy and, moreover, represents a considerable economic burden worldwide. All efforts at discovery new diagnostic and therapeutic tools last decades have invariably met with failure, making AD an incurable illness underscoring need approaches. In recent years, theranostic agents emerged as interesting strategy. They are molecules able simultaneously provide information deliver activity, allowing assessment molecule organism response pharmacokinetics. This makes these compounds promising streamlining research on drugs their application personalized medicine. We review here field small-molecule development novel resources against AD, highlighting positive significant impact that theranostics can be expected near future clinical practice.

Language: Английский

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Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches

Neuroscience Letters, Journal Year: 2023, Volume and Issue: 817, P. 137532 - 137532

Published: Oct. 20, 2023

Language: Английский

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Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights

Future Pharmacology, Journal Year: 2023, Volume and Issue: 3(4), P. 877 - 907

Published: Nov. 13, 2023

Alzheimer’s disease (AD) is a progressive, multifactorial, and unremitting neurodegenerative characterized by memory loss, personality changes, cognitive impairment. It has become more prevalent in recent years. Therefore, understanding the pathophysiology of AD developing efficient therapeutic strategies are essential. Moreover, progression unaffected pharmaceutical approaches discovered to date. Additionally, failure over 200 potential drug candidates clinical trials past decade suggests complexity difficulty both its underlying causes. research focused on medicinal plant-based natural products search for novel neuroprotective Indeed, several scientific investigations have demonstrated efficacy many plants their principal phytochemicals treatment AD. This review article covered pathophysiological mechanisms AD, necessity as anti-AD treatments, most preclinical studies revealing function bioactive compounds effective management In addition, also presents trial data promising formulations/agents plant origin. Revealing findings highlighting related development new treatments would promote further this field pave way safe debilitating disease.

Language: Английский

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Fluid biomarkers for the diagnosis of neurodegenerative diseases

Biomarkers in Neuropsychiatry, Journal Year: 2023, Volume and Issue: 8, P. 100062 - 100062

Published: March 23, 2023

In this review, we evaluate the role of fluid biomarkers related to neurodegenerative diseases. Such conditions present diagnostic challenges due phenotypic heterogeneity, longitudinal evolution, overlap between entities, and variability in progression. Biomarkers can potentially provide insight into diagnosis, progression, prognostication, treatment efficacy. This review covers recent advances including beta-amyloid, tau protein, neurofilament light chain, alpha-synuclein glial fibrillary briefly touches upon imaging biomarkers. For each biomarker, discuss pathophysiological correlates, clinical uses, accuracy, limitations.

Language: Английский

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GAP-43 closely interacts with BDNF in hippocampal neurons and is associated with Alzheimer's disease progression

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: April 18, 2023

Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity because it widely expressed at high levels in growth cones during axonal regeneration. GAP-43 mature adult neurons functionally important for the communication of synapses learning and memory. Brain-derived neurotrophic factor (BDNF) closely related to neurodegeneration synaptic aging process. However, molecular mechanisms regulating underlying pathogenesis progression Alzheimer's disease (AD) still remain incompletely understood. Remarkably, expressions BDNF perfectly match various Human Brain Atlas database. Moreover, are highly healthy adults' hippocampus brain region inversely correlated with amyloid beta (Aβ), which pathological peptide plaques found brains patients AD. These data led us investigate impact direct interaction between hippocampal neuron fate. In this study, we show that associated molecules AD (Tau Aβ). addition, define three-dimensional structure BDNF, including predictive binding sites via analysis using ClusPro 2.0, demonstrate deprivation triggers death memory dysfunction, employing or knock-down cellular models 5XFAD mice. results partners their signaling might be potential therapeutic targets

Language: Английский

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Developing a Two-Photon “AND” Logic Probe and Its Application in Alzheimer’s Disease Differentiation

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(46), P. 16868 - 16876

Published: Nov. 10, 2023

In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged hydrolysis neurotransmitter acetylcholine are relatively significantly altered. However, there few dual detection probes for butyrylcholinesterase. addition, single-response suffer from serious off-target effects near-infrared do not easily penetrate blood–brain barrier due to their excessive molecular weight. this work, we constructed a two-photon fluorescent probe that recognizes based on dual-lock strategy. The thiocarbonyl group is oxidized presence acid, occurs at 7-position ester bond existence butyrylcholinesterase, releasing strongly fluorophore, 4-methylumbelliferone. Excellent imaging was performed PC12 cells using probe, deep observed brains AD mice after tail vein injection with probe. It indicates can provide promising tool more precise diagnosis disease.

Language: Английский

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