Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

Cell, Год журнала: 2019, Номер 179(2), С. 312 - 339

Опубликована: Сен. 26, 2019

Язык: Английский

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Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning

Hippocampus, Год журнала: 2015, Номер 25(10), С. 1073 - 1188

Опубликована: Июль 2, 2015

ABSTRACT Sharp wave ripples (SPW‐Rs) represent the most synchronous population pattern in mammalian brain. Their excitatory output affects a wide area of cortex and several subcortical nuclei. SPW‐Rs occur during “off‐line” states brain, associated with consummatory behaviors non‐REM sleep, are influenced by numerous neurotransmitters neuromodulators. They arise from recurrent system CA3 region SPW‐induced excitation brings about fast network oscillation (ripple) CA1. The spike content is temporally spatially coordinated consortium interneurons to replay fragments waking neuronal sequences compressed format. assist transferring this hippocampal representation distributed circuits support memory consolidation; selective disruption interferes memory. Recently acquired pre‐existing information combined SPW‐R influence decisions, plan actions and, potentially, allow for creative thoughts. In addition widely studied contribution memory, may also affect endocrine function via activation hypothalamic circuits. Alteration physiological mechanisms supporting leads their pathological conversion, “p‐ripples,” which marker epileptogenic tissue can be observed rodent models schizophrenia Alzheimer's Disease. Mechanisms genesis discussed review. © 2015 Authors Hippocampus Published Wiley Periodicals, Inc.

Язык: Английский

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Sleep and Human Aging

Neuron, Год журнала: 2017, Номер 94(1), С. 19 - 36

Опубликована: Апрель 1, 2017

Язык: Английский

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Generation of circadian rhythms in the suprachiasmatic nucleus

Nature reviews. Neuroscience, Год журнала: 2018, Номер 19(8), С. 453 - 469

Опубликована: Июнь 22, 2018

Язык: Английский

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Sleep and Alzheimer disease pathology—a bidirectional relationship

Nature Reviews Neurology, Год журнала: 2013, Номер 10(2), С. 115 - 119

Опубликована: Дек. 24, 2013

Язык: Английский

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Network abnormalities and interneuron dysfunction in Alzheimer disease

Nature reviews. Neuroscience, Год журнала: 2016, Номер 17(12), С. 777 - 792

Опубликована: Ноя. 10, 2016

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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The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade

Journal of Alzheimer s Disease, Год журнала: 2018, Номер 64(s1), С. S567 - S610

Опубликована: Июнь 12, 2018

The amyloid-␤ oligomer (A␤O) hypothesis was introduced in 1998.It proposed that the brain damage leading to Alzheimer's disease (AD) instigated by soluble, ligand-like A␤Os.This based on discovery fibril-free synthetic preparations of A␤Os were potent CNS neurotoxins rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998).The mechanism attributed disrupted signaling involving tyrosine-protein kinase Fyn, mediated an unknown toxin receptor.Over 4,000 articles concerning have been published since then, including more than 400 reviews.A␤Os shown accumulate AD-dependent manner human and animal model tissue experimentally, impair learning memory instigate major facets AD neuropathology, tau pathology, synapse deterioration loss, inflammation, oxidative damage.As reviewed Hayden Teplow 2013, A␤O "has all but supplanted amyloid cascade."Despite emerging understanding role played pathogenesis, not yet received clinical attention given plaques, which at core attempts therapeutics diagnostics are no longer regarded as most pathogenic form A␤.However, if momentum research continues, particularly efforts elucidate key aspects structure, a clear path successful modifying therapy can be envisioned.Ensuring lessons learned from recent, late-stage failures applied appropriately throughout therapeutic development will further enable likelihood near-term.

Язык: Английский

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Mechanisms linking circadian clocks, sleep, and neurodegeneration

Science, Год журнала: 2016, Номер 354(6315), С. 1004 - 1008

Опубликована: Ноя. 24, 2016

Disruptions of normal circadian rhythms and sleep cycles are consequences aging can profoundly affect health. Accumulating evidence indicates that disturbances, which have long been considered symptoms many neurodegenerative conditions, may actually drive pathogenesis early in the course these diseases. In this Review, we explore potential cellular molecular mechanisms linking dysfunction loss to diseases, with a focus on Alzheimer’s disease. We examine interplay between central peripheral rhythms, clock gene function, maintaining brain homeostasis, discuss therapeutic implications. The influence number key processes involved neurodegeneration, suggesting systems might be manipulated promote healthy aging.

Язык: Английский

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Sleep Quality and Preclinical Alzheimer Disease

JAMA Neurology, Год журнала: 2013, Номер 70(5), С. 587 - 587

Опубликована: Март 11, 2013

Sleep and circadian problems are very common in Alzheimer disease (AD). Recent animal studies suggest a bidirectional relationship between sleep β-amyloid (Aβ), key molecule involved AD pathogenesis.To test whether Aβ deposition preclinical AD, prior to the appearance of cognitive impairment, is associated with changes quality or quantity sleep.Cross-sectional study conducted from October 2010 June 2012.General community volunteers at Washington University Knight Alzheimer's Disease Research Center.Cognitively normal individuals (n = 145) 45 years older were recruited longitudinal memory aging Center. Valid actigraphy data recorded 142. The majority (124 142) Adult Children Study, which all aged 75 baseline 50% have parental history late-onset AD. rest volunteer cohort than 60 healthy baseline.Sleep was objectively measured using for 2 weeks. efficiency, percentage time bed spent asleep, primary measure quality. Total quantity. Cerebrospinal fluid Aβ42 levels used determine amyloid present absent. Concurrent diaries provided nap information.Amyloid deposition, as assessed by levels, 32 participants (22.5%). This group had worse quality, efficiency (80.4% vs 83.7%), compared those without after correction age, sex, APOEε4 allele carrier status (P .04). In contrast, not significantly different groups, total time. Frequent napping, 3 more days per week, (31.2% 14.7%; P .03).Amyloid stage appears be but

Язык: Английский

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