Alzheimer’s Disease: Epidemiology and Clinical Progression

Neurology and Therapy, Год журнала: 2022, Номер 11(2), С. 553 - 569

Опубликована: Март 14, 2022

Alzheimer’s disease (AD) is prevalent throughout the world and leading cause of dementia in older individuals (aged ≥ 65 years). To gain a deeper understanding recent literature on epidemiology AD its progression, we conducted review PubMed-indexed (2014–2021) North America, Europe, Asia. The worldwide toll evidenced by rising prevalence, incidence, mortality due to AD—estimates which are low because underdiagnosis AD. Mild cognitive impairment (MCI) can ultimately progress dementia; estimates etiology among patients with MCI range from 40% 75% depending populations studied whether diagnosis was made clinically or combination biomarkers. risk increases progression normal cognition no amyloid-beta (Aβ) accumulation early neurodegeneration subsequently MCI. For Aβ neurodegeneration, lifetime has been estimated be 41.9% women 33.6% men. Data preclinical sparse, but an analysis across three National Institute Aging Association (NIA-AA) stages suggests that NIA-AA stage 3 (subtle decline biomarker positivity) could useful other tools for treatment decision-making. Factors shown increase include lower Mini-Mental State Examination (MMSE) score, higher Disease Assessment Scale (ADAS-cog) positive APOE4 status, white matter hyperintensities volume, entorhinal cortex atrophy, cerebrospinal fluid (CSF) total tau, CSF neurogranin levels, dependency instrumental activities daily living (IADL), being female. Results suggest use biomarkers alongside neurocognitive tests will become important part clinical practice as new disease-modifying therapies introduced.

Язык: Английский

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Heterogeneity in Alzheimer's Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials

Neurotherapeutics, Год журнала: 2022, Номер 19(1), С. 8 - 25

Опубликована: Янв. 1, 2022

Язык: Английский

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Aptamer-Functionalized Carbon Nanotube Field-Effect Transistor Biosensors for Alzheimer’s Disease Serum Biomarker Detection

ACS Sensors, Год журнала: 2022, Номер 7(7), С. 2075 - 2083

Опубликована: Июль 11, 2022

Blood-biomarker-based tests are highly important for the early clinical diagnosis of Alzheimer's disease (AD) and treatment care AD patients, but complex serum environment extremely low abundance blood protein biomarkers present challenges. Nanomaterials promising constructing sensitive transistor-based biosensors due to their small size. However, such difficult fabricate on a large scale suffer from lack combined optimization reproducibility sensitivity in physiological fluids. In this work, field-effect transistor (FET) based uniform semiconducting carbon nanotube (CNT) thin films mass produced achieve selective detection core β-amyloid (Aβ). The combination mass-produced CNT FET sensors oligonucleotide aptamers as efficient bioreceptors enables reliable reproducible sub-femtomolar full human Aβ42 Aβ40 peptides has outperformed other methods reported date. adsorption biological substrates sensor was significantly reduced by multiple blocking steps, resulting selectivity ratios up 730% (Aβ40) 800% (Aβ42). aptamer-functionalized biosensor exhibits dynamic range (>104), rapid response time (several minutes), variation (<10%) can be delivered low-cost technology screening AD. This platform will help bring laboratory-based expensive diagnostic tools point care.

Язык: Английский

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Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Май 15, 2024

Abstract Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades research clinical investigation. This might be partly due a lack widely available cost-effective modalities for diagnosis prognosis. Recently, blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity precision assays measurement platforms. Several biomarkers have shown high potential accurately detecting pathophysiology. As result, there been considerable interest in applying these prognosis, as surrogate metrics investigate impact various covariates on pathophysiology accelerate therapeutic trials monitor treatment effects. However, standardization how blood samples collected, processed, stored analyzed reported can affect reproducibility measurements, potentially hindering toward their widespread use settings. To help address issues, we provide fundamental guidelines developed according recent findings sample handling measurements. These cover important considerations including study design, collection, processing, biobanking, measurement, result reporting. Furthermore, proposed include best practices appropriate procedures genetic ribonucleic acid analyses. While focus key AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau glial fibrillary acidic protein), anticipate that will generally applicable other types biomarkers. We also assist investigators planning executing research, enabling harmonization improve comparability across studies.

Язык: Английский

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Blood phosphorylated Tau181 reliably differentiates amyloid‐positive from amyloid‐negative subjects in the Alzheimer's disease continuum: A systematic review and meta‐analysis

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 1, 2025

Abstract INTRODUCTION Blood‐based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD). METHODS We performed a systematic review and meta‐analysis on potential blood phosphorylated Tau181 (p‐tau181) to differentiate amyloid‐positive (A+) amyloid‐negative (A−) subjects. Two meta‐analyses were conducted, showing mean p‐tau values in cerebrospinal fluid (CSF) A+ A− group, second comparing concentrations CSF among versus A‐ participants, by laboratory assessment method. RESULTS Eighteen studies (2764 5646 subjects) included. The single‐group showed higher p‐tau181 than group. In head‐to‐head meta‐analysis, reliably differentiated patients from participants. DISCUSSION Regardless technique, differentiates Therefore, it might have important applications early inclusion clinical trials AD patients. Highlights role blood‐based discriminating is still uncertain. Blood distinguishes allow trials.

Язык: Английский

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Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment

Antioxidants, Год журнала: 2021, Номер 11(1), С. 87 - 87

Опубликована: Дек. 30, 2021

Allicin (diallylthiosulfinate) is a defense molecule produced by cellular contents of garlic (Allium sativum L.). On tissue damage, the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) converted to allicin in an enzyme-mediated process catalysed alliinase. hydrophobic nature, can efficiently cross membranes and behaves as reactive sulfur species (RSS) inside cells. It physiologically active with ability oxidise thiol groups glutathione between cysteine residues proteins. has shown anticancer, antimicrobial, antioxidant properties also serves efficient therapeutic agent against cardiovascular diseases. In this context, present review describes antioxidant, neuroprotective that ameliorate cognitive abilities case neurodegenerative neuropsychological disorders. As fights oxygen (ROS) downregulation NOX (NADPH oxidizing) enzymes, it directly interact reduce levels different types ROS variety peroxidases. Most actions are mediated via redox-dependent pathways. inhibits neuroinflammation suppressing production, inhibition TLR4/MyD88/NF-κB, P38 JNK inhibitor cholinesterase (AChE) butyrylcholinesterase (BuChE) be applied manage Alzheimer’s disease, helps maintain balance neurotransmitters autism spectrum disorder (ASD) attention deficit hyperactive syndrome (ADHD). acute traumatic spinal cord injury (SCI) protects neuron damage regulating inflammation, apoptosis promoting expression Nrf2 (nuclear factor erythroid 2-related 2). Metal induced neurodegeneration attenuated patients suffering from neurological diseases ameliorates administration.

Язык: Английский

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β-Amyloid in blood neuronal-derived extracellular vesicles is elevated in cognitively normal adults at risk of Alzheimer’s disease and predicts cerebral amyloidosis

Alzheimer s Research & Therapy, Год журнала: 2022, Номер 14(1)

Опубликована: Май 12, 2022

Abstract Background Blood biomarkers that can be used for preclinical Alzheimer’s disease (AD) diagnosis would enable trial enrollment at a time when the is potentially reversible. Here, we investigated plasma neuronal-derived extracellular vesicle (nEV) cargo in patients along continuum, focusing on cognitively normal controls (NCs) with high brain β-amyloid (Aβ) loads (Aβ+). Methods The study was based Sino Longitudinal Study Cognitive Decline project. We enrolled 246 participants, including 156 NCs, 45 amnestic mild cognitive impairment (aMCI) patients, and AD dementia (ADD) patients. Brain Aβ were determined using positron emission tomography. NCs classified into 84 Aβ− 72 Aβ+ NCs. Baseline nEVs isolated by immunoprecipitation an anti-CD171 antibody. After verification, their cargos, Aβ, tau phosphorylated threonine 181, neurofilament light, quantified single-molecule array. Concentrations of these cargos compared among groups, receiver operating characteristic (ROC) curves constructed. A subset participants underwent follow-up assessment magnetic resonance imaging. relationships nEV levels amyloid deposition, longitudinal changes cognition, regional volume explored correlation analysis. Additionally, 458 subjects project had previously undergone quantification. Results Only included subsequent focused 42 current study. normalization nEVs, found to increase gradually across lowest NC group, further aMCI highest ADD contributing diagnoses (Aβ− vs. area under ROC curve values 0.663; aMCI, 0.857; ADD, 0.957). Furthermore, significantly correlated as well cognition entorhinal volume. There no differences individuals. Conclusions Our findings suggest potential use diagnosing AD-induced This biomarker reflects cortical deposition predicts decline atrophy.

Язык: Английский

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Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Сен. 28, 2022

Alzheimer's disease (AD) is the most common neurodegenerative and its pathogenesis still unclear. There dysbiosis of gut microbiota in AD patients. More importantly, has been observed not only patients, but also patients with mild cognitive impairment (MCI). However, mechanism poorly understood. Cholinergic anti-inflammatory pathway an important for central nervous system (CNS) regulation peripheral immune homeostasis, especially gut. Therefore, we speculated that dysfunction cholinergic a potential AD.In this study, constructed model mice by injecting Aβ1-42 into lateral ventricle, detected level Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect abundance each group at baseline, 2 weeks 4 after surgery. Furthermore, immunofluorescence western blot were alteration intestinal structure mice, pathway, APP process brain colon group.Aβ1-42 i.c.v induced neuron damage mice. At same time, surgery, while there no difference baseline changes increased levels pro-inflammatory factors treatment group, accompanied inhibition pathways. Amyloidogenic pathways both accelerated group.The present findings suggested Aβ CNS can induce dysbiosis, alter accelerate amyloidogenic pathways, which related inhibiting

Язык: Английский

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Oxidative Stress in Brain in Amnestic Mild Cognitive Impairment

Antioxidants, Год журнала: 2023, Номер 12(2), С. 462 - 462

Опубликована: Фев. 11, 2023

Amnestic mild cognitive impairment (MCI), arguably the earliest clinical stage of Alzheimer disease (AD), is characterized by normal activities daily living but with memory issues no dementia. Oxidative stress, consequent damaged key proteins and lipids, are prominent even in this early state AD. This review article outlines oxidative stress MCI how can account for neuronal loss potential therapeutic strategies to slow progression

Язык: Английский

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Which neuroimaging and fluid biomarkers method is better in theranostic of Alzheimer’s disease? An umbrella review

IBRO Neuroscience Reports, Год журнала: 2024, Номер 16, С. 403 - 417

Опубликована: Фев. 29, 2024

Язык: Английский

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