Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

Molecules, Год журнала: 2020, Номер 25(24), С. 5789 - 5789

Опубликована: Дек. 8, 2020

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in brain and it main cause dementia, which characterized by decline thinking independence personal daily activities. AD considered multifactorial disease: two hypotheses were proposed as for AD, cholinergic amyloid hypotheses. Additionally, several risk factors such increasing age, genetic factors, head injuries, vascular diseases, infections, environmental play role disease. Currently, there are only classes approved drugs to treat including inhibitors cholinesterase enzyme antagonists N-methyl d-aspartate (NMDA), effective treating symptoms but do not cure or prevent Nowadays, research focusing on understanding pathology targeting mechanisms, abnormal tau protein metabolism, β-amyloid, inflammatory response, free radical damage, aiming develop successful treatments capable stopping modifying course AD. This review discusses currently available future theories development new therapies disease-modifying therapeutics (DMT), chaperones, natural compounds.

Язык: Английский

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Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology

Acta Neuropathologica, Год журнала: 2021, Номер 141(5), С. 709 - 724

Опубликована: Фев. 14, 2021

Abstract The quantification of phosphorylated tau in biofluids, either cerebrospinal fluid (CSF) or plasma, has shown great promise detecting Alzheimer’s disease (AD) pathophysiology. Tau at threonine 231 (p-tau231) is one such biomarker CSF but its usefulness as a blood currently unknown. Here, we developed an ultrasensitive Single molecule array (Simoa) for the plasma p-tau231 which was validated four independent cohorts ( n = 588) different settings, including full AD continuum and non-AD neurodegenerative disorders. Plasma able to identify patients with differentiate them from amyloid-β negative cognitively unimpaired (CU) older adults high accuracy (AUC 0.92–0.94). also distinguished disorders 0.93), well MCI 0.89). In neuropathology cohort, samples taken on avergae 4.2 years prior post-mortem very accurately identified comparison 0.99), this despite all being given dementia diagnosis during life. highly correlated p-tau231, pathology assessed by [ 18 F]MK-6240 positron emission tomography (PET), brain amyloidosis F]AZD469 PET. Remarkably, inflection point increasing function continuous PET standardized uptake value ratio, be earlier than standard thresholds positivity increase p-tau181. Furthermore, significantly increased quartiles 2–4, whereas p-tau217 p-tau181 only 3–4 4, respectively. Finally, differentiated individuals across entire Braak stage spectrum, staging 0 through I–II, not observed To conclude, novel assay identifies clinical stages equally p-tau181, increases earlier, already subtle deposition, threshold been attained, response early deposition. Thus, promising emerging potential facilitate trials vulnerable populations below apparent entorhinal

Язык: Английский

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The China Alzheimer Report 2022

General Psychiatry, Год журнала: 2022, Номер 35(1), С. e100751 - e100751

Опубликована: Фев. 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.

Язык: Английский

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Developing the ATX(N) classification for use across the Alzheimer disease continuum

Nature Reviews Neurology, Год журнала: 2021, Номер 17(9), С. 580 - 589

Опубликована: Июль 8, 2021

Язык: Английский

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Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer’s disease: a systematic review

Ageing Research Reviews, Год журнала: 2021, Номер 72, С. 101496 - 101496

Опубликована: Окт. 22, 2021

Alzheimer's disease (AD) is the most prevalent neurodegenerative in ageing, affecting around 46 million people worldwide but few treatments are currently available. The etiology of AD still puzzling, and new drugs development clinical trials have high failure rates. Urgent outline an integral (multi-target) effective treatment needed. Accumulation amyloid-β (Aβ) peptides considered one fundamental neuropathological pillars disease, its dyshomeostasis has shown a crucial role onset. Therefore, many amyloid-targeted therapies been investigated. Here, we will systematically review recent (from 2014) investigational, follow-up studies focused on anti-amyloid strategies to summarize analyze their current potential. Combination anti-Aβ with developing early detection biomarkers other therapeutic agents acting functional changes be highlighted this review. Near-term approval seems likely for several against Aβ, FDA monoclonal oligomers antibody –aducanumab– raising hopes controversies. We conclude that, oligomer-epitope specific Aβ implementation multiple improved risk prediction methods allowing detection, together factors such as hyperexcitability AD, could key slowing global pandemic.

Язык: Английский

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Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer’s Disease: A Focus on Aducanumab and Lecanemab

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Апрель 12, 2022

Alzheimer's disease (AD) is the most prevalent form of age-related dementia in world, and its main pathological features consist amyloid-β (Aβ) plaque deposits neurofibrillary tangles formed by hyperphosphorylated tau protein. So far, only a few AD treatments approved have been applied clinic, but effects these drugs are limited for partial symptomatic relief to patients with unable alter progression. Later, all efforts targeting pathogenic factors were unsuccessful over past decades, which suggested that pathogenesis complex. Recently, disease-modifying therapies (DMTs) can change underlying pathophysiology AD, anti-Aβ monoclonal antibodies (mabs) (e.g., aducanumab, bapineuzumab, gantenerumab, solanezumab, lecanemab) developed successively conducted clinical trials based on theory systemic failure cell-mediated Aβ clearance contributes occurrence In review, we summarized recent studies therapeutic trial results mabs AD. Specifically, focused discussion impact aducanumab lecanemab pathology profiles. The review provides possible evidence applying immunotherapy analyzes lessons learned from order further study adverse

Язык: Английский

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Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Язык: Английский

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Amyloid Beta in Aging and Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 12924 - 12924

Опубликована: Окт. 26, 2022

Alzheimer’s disease (AD), is a progressive neurodegenerative that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs two forms, early onset familial late-onset sporadic; genetic mutations PS1, PS2, APP genes cause AD, combination of lifestyle, environment factors causes the sporadic form disease. However, accelerated progression noticed patients with AD. Disease-causing pathological changes are synaptic damage, mitochondrial structural functional changes, addition to increased production accumulation phosphorylated tau (p-tau), amyloid beta (Aβ) affected brain regions patients. Aβ peptide derived from precursor protein (APP) by proteolytic cleavage gamma secretases. glycoprotein plays significant role maintaining neuronal homeostasis like signaling, development, intracellular transport. reported have both protective toxic effects neurons. The purpose our article summarize recent developments its association synapses, mitochondria, microglia, astrocytes, interaction p-tau. Our also covers therapeutic strategies reduce toxicities discusses reasons for failures therapeutics.

Язык: Английский

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Amyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease

Neural Regeneration Research, Год журнала: 2021, Номер 17(8), С. 1666 - 1666

Опубликована: Дек. 10, 2021

Alzheimer's disease is a neurodegenerative that accounts for most of the 50-million dementia cases worldwide in 2018. A large amount evidence supports amyloid cascade hypothesis, which states amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation form neurofibrillary tangles, these aggregates lead to inflammation, synaptic impairment, neuronal loss, thus cognitive decline behavioral abnormalities. The poor correlation found between plaques, have led scientific community question whether actually triggering neurodegeneration disease. occurrence tangles better correlates loss clinical symptoms and, although may initiate events, impairment likely effector molecule neurodegeneration. Recently, it has been shown cooperatively work impair transcription genes involved function more importantly, downregulation partially reverses transcriptional perturbations. Despite mounting points an interplay tau, some factors could independently affect both pathologies. Thus, dual pathway there are common upstream causing abnormalities proposed. Among others, immune system seems be strongly Other factors, as apolipoprotein E ε4 isoform suggested act link hyperphosphorylation. Interestingly, amyloid-beta-immunotherapy reduces not only but also levels animal models trials. Likewise, tau-immunotherapy levels. even though immunotherapy advanced than tau-immunotherapy, combined tau-directed therapies at early stages recently proposed strategy stop progression

Язык: Английский

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Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease

Molecular Biology Reports, Год журнала: 2021, Номер 48(7), С. 5629 - 5645

Опубликована: Июнь 28, 2021

Язык: Английский

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