Alzheimer's disease

The Lancet, Journal Year: 2021, Volume and Issue: 397(10284), P. 1577 - 1590

Published: March 2, 2021

Language: Английский

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Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease

Current Neuropharmacology, Journal Year: 2020, Volume and Issue: 18(11), P. 1106 - 1125

Published: May 28, 2020

The only conclusive way to diagnose Alzheimer's is carry out brain autopsy of the patient's tissue and ascertain whether subject had or any other form dementia. However, due non-feasibility such methods, conclude conditions, medical practitioners use tests that examine a mental ability.Accurate diagnosis at an early stage need hour for initiation therapy. cause most cases still remains unknown except where genetic distinctions have been observed. Thus, standard drug regimen ensues in every patient, irrespective cause, which may not always be beneficial halting reversing disease progression. To provide better life patients by suppressing existing symptoms, diagnosis, curative therapy, site-specific delivery drugs, application hyphenated methods like artificial intelligence brought into main field therapeutics.In this review, we compiled hypotheses explain disease, highlighted gene immunotherapy, peptidomimetics, metal chelators, probiotics quantum dots as advancements strategies manage Alzheimer's.Biomarkers, brain-imaging, theranostics, along with intelligence, are understood future management Alzheimer's.

Language: Английский

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Blood-based biomarkers for Alzheimer's disease: towards clinical implementation

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 21(1), P. 66 - 77

Published: Nov. 25, 2021

Language: Английский

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The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(12), P. 3824 - 3824

Published: Nov. 30, 2018

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and considered to be peculiarity professional phagocytic cells. Over the last decade, several more homologs have been identified based on current research, NOX family consists NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 DUOX2 enzymes. NOXs are electron transporting membrane proteins that responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also generated. Elevated ROS leads oxidative stress (OS), which has associated myriad inflammatory degenerative pathologies. Interestingly, OS is commonality in pathophysiology neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS) multiple (MS). enzymes expressed neurons, glial cells cerebrovascular endothelial NOX-mediated one main causes damage diseases. In this review, we will discuss recent developments our understanding mechanisms linking activity, diseases, particular focus neurovascular component these conditions. We conclude highlighting challenges future opportunities combat age-related disorders by targeting NOXs.

Language: Английский

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Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Annals of Neurology, Journal Year: 2018, Volume and Issue: 84(5), P. 648 - 658

Published: Sept. 9, 2018

Objective We investigated the association of plasma amyloid beta (Abeta)40, Abeta42, and total tau (tTau) with presence Alzheimer pathological changes in cognitively normal individuals subjective cognitive decline (SCD). Methods included 248 subjects SCD (61 ± 9 years, 42% female, Mini‐Mental State Examination = 28 2) from SCIENCe project Amsterdam Dementia Cohort. Subjects were dichotomized as abnormal by cerebrospinal fluid (CSF) positron emission tomography (PET). Baseline Abeta40, tTau measured using Simoa technology. Associations between levels status assessed logistic regression analyses receiver operating characteristic analyses. Association risk clinical progression to mild impairment (MCI) or dementia was Cox proportional hazard models. Results Fifty‐seven (23%) CSF‐amyloid abnormal. Plasma Abeta42/Abeta40 ratio Abeta42 alone, but not tTau, identified (plasma ratio: area under curve [AUC] 77%, 95% confidence interval [CI] 69–84%; Abeta42: AUC 66%, CI: 58–74%). Combining age apolipoprotein E resulted 83% (95% CI 77–89%). The Youden cutoff gave a sensitivity 76% specificity 75%, applying this prescreener would reduce number lumbar punctures 51%. Using PET outcome, comparable reduction scans be achieved when prescreener. In addition, low associated MCI (hazard 2.0, 1.4–2.3). Interpretation has potential identify SCD. Ann Neurol 2018;84:656–666

Language: Английский

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The China Alzheimer Report 2022

General Psychiatry, Journal Year: 2022, Volume and Issue: 35(1), P. e100751 - e100751

Published: Feb. 1, 2022

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) related dementias (ADRD). AD's incidence rate, morbidity, mortality steadily increased to make it presently fifth leading cause death among urban rural residents in China magnify resulting financial burdens on individuals, families society. The 'Healthy Action' plan 2019-2030 promotes transition from treatment health maintenance for this expanding with ADRD. This report describes epidemiological trends, evaluates burden disease, outlines current clinical diagnosis status delineates existing available public resources. More specifically, examines impact ADRD, including prevalence, mortality, costs, usage care, overall effect caregivers In addition, special presents technical guidance supports prevention AD, provides expertise guide relevant governmental healthcare policy suggests an information platform international exchange cooperation.

Language: Английский

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Association of Extracellular Vesicle Biomarkers With Alzheimer Disease in the Baltimore Longitudinal Study of Aging

JAMA Neurology, Journal Year: 2019, Volume and Issue: 76(11), P. 1340 - 1340

Published: July 15, 2019

Blood biomarkers able to diagnose Alzheimer disease (AD) at the preclinical stage would enable trial enrollment when is potentially reversible. Plasma neuronal-enriched extracellular vesicles (nEVs) of patients with AD were reported exhibit elevated levels phosphorylated (p) tau, Aβ42, and insulin receptor substrate 1 (IRS-1).To validate nEV as predictors.This case-control study included longitudinal plasma samples from cognitively normal participants in Baltimore Longitudinal Study Aging (BLSA) cohort who developed up January 2015 age- sex-matched controls remained over a similar length follow-up. Repeated blindly analyzed year clinical Johns Hopkins Disease Research Center (JHADRC). Data collected September 2016 2018. Analyses conducted March 2019.Neuronal-enriched immunoprecipitated; IRS-1 quantified by immunoassays; concentration diameter determined nanoparticle tracking analysis. Levels trajectories between future control compared.Overall, 887 128 BLSA eventually 222 age analyzed. Participants followed (from earliest sample symptom onset) for mean (SD) 3.5 (2.31) years (range, 0-9.73 years). Overall, 161 training set, 80 test set. (mean [SD] age, 79.09 [7.02] years; 68 women [53.13%]) had longitudinally higher p-tau181, p-tau231, pSer312-IRS-1, pY-IRS-1, than 76.2 [7.36] 110 [50.45%]) but total TSG101, concentration. In model combining data achieved 89.6% area under curve (AUC), 81.8% sensitivity, 85.8% specificity predicting AD. The was validated set (80% AUC, 55.6% 88.7% specificity). Preclinical associated cognitive performance. addition, repeated 64 JHADRC (35 AD: 74.03 [8.73] 18 [51.43%] 29 controls: 72.14 [7.86] 23 [79.31%]), discrimination 98.9% 100% 94.7% 76.7% 91.7% 60% set.We biomarker candidates further demonstrated that their can predict diagnosis. These findings motivate development toward blood

Language: Английский

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Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology

Alzheimer s Research & Therapy, Journal Year: 2020, Volume and Issue: 12(1)

Published: Sept. 28, 2020

Abstract Background Blood-based biomarkers for Alzheimer’s disease (AD) might facilitate identification of participants clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential plasma markers Abeta (1-42/1-40) , glial fibrillary acidic protein (GFAP) neurofilament light (NfL) to identify cerebral amyloidosis and/or severity. Methods included individuals with a positive ( n = 176: 63 ± 7 years, 87 (49%) females) or negative 76: 61 9 27 (36%) PET status, syndrome diagnosis subjective cognitive decline (18 PET+, 25 PET−), mild impairment (26 24 AD-dementia (132 PET+). Plasma GFAP, NfL were measured by Simoa. applied two-way ANOVA adjusted age sex investigate associations status diagnosis; logistic regression analysis Wald’s backward selection an optimal panel that identifies positivity; age, sex, education-adjusted linear between neuropsychological test performance; Spearman’s correlation medial temporal lobe atrophy (MTA). Results GFAP independently associated p 0.009 < 0.001 respectively), 0.048 respectively). The identifying alongside APOE (AUC 88% (95% CI 83–93%), 82% sensitivity, 86% specificity), while excluding sex. robustly performance on global cognition all major domains (GFAP: range standardized β (sβ) − 0.40 0.26; NfL: sβ 0.35 0.18; all: 0.002), whereas cognition, memory, attention, executive functioning (range 0.22 – 0.11; 0.05) but not language. showed moderate correlations MTA (both: rho> 0.33, 0.001). (Spearman’s rho 0.24, Discussion conclusions Combination provides valuable tool status. Furthermore, associate various severity measures suggesting monitoring.

Language: Английский

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Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2019, Volume and Issue: 15(6), P. 764 - 775

Published: May 18, 2019

Abstract Introduction Blood‐based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large‐scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials management. Methods We investigated whether plasma concentrations the Aβ 1–40 /Aβ 1–42 ratio, assessed using single‐molecule array (Simoa) immunoassay, may predict positron emission tomography status in a longitudinal monocentric cohort (N = 276) older individuals with subjective memory complaints. performed hypothesis‐driven investigation followed by no‐a‐priori hypothesis study machine learning. Results The receiver operating characteristic curve learning showed balanced accuracy 76.5% 81%, respectively, ratio. is not affected apolipoprotein E ( APOE ) ε4 allele, sex, or age. Discussion Our results encourage an independent validation confirm indication that via Simoa, improve future standard care trial design.

Language: Английский

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Early-Onset Alzheimer’s Disease: What Is Missing in Research?

Current Neurology and Neuroscience Reports, Journal Year: 2021, Volume and Issue: 21(2)

Published: Jan. 19, 2021

Early-onset Alzheimer's disease (EOAD), defined as (AD) occurring before age 65, is significantly less well studied than the late-onset form (LOAD) despite EOAD often presenting with a more aggressive progression. The aim of this review to summarize current understanding etiology EOAD, their translation into clinical practice, and suggest steps be taken move our forward.

Language: Английский

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