Alzheimer disease

Nature Reviews Disease Primers, Год журнала: 2021, Номер 7(1)

Опубликована: Май 13, 2021

Язык: Английский

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Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease

Frontiers in Neuroscience, Год журнала: 2018, Номер 12

Опубликована: Янв. 30, 2018

The so-called amyloid hypothesis, that the accumulation and deposition of oligomeric or fibrillar β (Aβ) peptide is primary cause Alzheimer's disease (AD), has been mainstream concept underlying AD research for over 20 years. However, all attempts to develop Aβ-targeting drugs treat have ended in failure. Here, we review recent findings indicating main factor development progression tau, not Aβ, describe deficiencies hypothesis supported emergence this idea.

Язык: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Июль 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Язык: Английский

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Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Язык: Английский

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Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies

Nature Reviews Neurology, Год журнала: 2017, Номер 14(1), С. 22 - 39

Опубликована: Дек. 15, 2017

Язык: Английский

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The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

Acta Neuropathologica, Год журнала: 2020, Номер 140(4), С. 417 - 447

Опубликована: Июль 29, 2020

Abstract Tau and amyloid beta (Aβ) are the prime suspects for driving pathology in Alzheimer’s disease (AD) and, as such, have become focus of therapeutic development. Recent research, however, shows that these proteins been highly conserved throughout evolution may crucial, physiological roles. Such functions be lost during AD progression or unintentionally disrupted by tau- Aβ-targeting therapies. has revealed to more than a simple stabiliser microtubules, reported play role range biological processes including myelination, glucose metabolism, axonal transport, microtubule dynamics, iron homeostasis, neurogenesis, motor function, learning memory, neuronal excitability, DNA protection. Aβ is similarly multifunctional, proposed regulate angiogenesis, repair leaks blood–brain barrier, promote recovery from injury, act an antimicrobial peptide tumour suppressor. This review will discuss potential roles tau Aβ, highlighting how changes contribute pathology, well implications We propose balanced consideration both pathological essential design safe effective therapeutics.

Язык: Английский

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Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases

Science, Год журнала: 2020, Номер 370(6512), С. 66 - 69

Опубликована: Окт. 2, 2020

Dementia is a rapidly rising global health crisis that silently disables families and ends lives livelihoods around the world. To date, however, no early biomarkers or effective therapies exist. It now clear brain microglia are more than mere bystanders amyloid phagocytes; they can act as governors of neuronal function homeostasis in adult brain. Here, we highlight fundamental role tissue-resident macrophages health. Then, suggest how chronic impairment microglia-neuron cross-talk may secure permanence failure synaptic Alzheimer's Parkinson's diseases. Understanding to assess modulate interactions critical for will be key developing dementia.

Язык: Английский

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The complexity of tau in Alzheimer’s disease

Neuroscience Letters, Год журнала: 2019, Номер 705, С. 183 - 194

Опубликована: Апрель 25, 2019

Язык: Английский

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Synaptic degeneration in Alzheimer disease

Nature Reviews Neurology, Год журнала: 2022, Номер 19(1), С. 19 - 38

Опубликована: Дек. 13, 2022

Язык: Английский

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Mechanisms of secretion and spreading of pathological tau protein

Cellular and Molecular Life Sciences, Год журнала: 2019, Номер 77(9), С. 1721 - 1744

Опубликована: Окт. 30, 2019

Abstract Accumulation of misfolded and aggregated forms tau protein in the brain is a neuropathological hallmark tauopathies, such as Alzheimer’s disease frontotemporal lobar degeneration. Tau aggregates have ability to transfer from one cell another induce templated misfolding aggregation healthy molecules previously cells, thereby propagating pathology across different areas prion-like manner. The molecular mechanisms involved cell-to-cell are diverse, not mutually exclusive only partially understood. Intracellular accumulation induces several that aim reduce cellular burden proteins also promote secretion aggregates. However, may be released cells physiologically unrelated aggregation. involves multiple vesicular non-vesicle-mediated pathways, including directly through plasma membrane. Consequently, extracellular can found various forms, both free vesicles, exosomes ectosomes. Once space, internalized by neighboring neurons glial via endocytic, pinocytic phagocytic mechanisms. Importantly, accumulating evidence suggests propagation could provide general mechanism for progression tauopathies other related neurodegenerative diseases. Here, we review recent literature on tau, with particular focus secretion.

Язык: Английский

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