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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Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Science, Год журнала: 2019, Номер 366(6465), С. 628 - 631

Опубликована: Окт. 31, 2019

Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related not known. We used accelerated neuroimaging measure physiological dynamics human discovered a coherent pattern oscillating electrophysiological, hemodynamic, CSF that appears during non-rapid eye movement sleep. Neural slow followed by hemodynamic oscillations, which turn coupled flow. These results demonstrate sleeping exhibits flow on macroscopic scale, interlinked with rhythms.

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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Glymphatic failure as a final common pathway to dementia

Science, Год журнала: 2020, Номер 370(6512), С. 50 - 56

Опубликована: Окт. 2, 2020

Sleep is evolutionarily conserved across all species, and impaired sleep a common trait of the diseased brain. quality decreases as we age, disruption regular architecture frequent antecedent to onset dementia in neurodegenerative diseases. The glymphatic system, which clears brain protein waste products, mostly active during sleep. Yet system degrades with suggesting causal relationship between disturbance symptomatic progression dementias. ties that bind sleep, aging, clearance, aggregation have shed new light on pathogenesis broad range diseases, for failure may constitute therapeutically targetable final pathway.

Язык: Английский

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Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways

Nature Reviews Neurology, Год журнала: 2019, Номер 16(1), С. 30 - 42

Опубликована: Дек. 11, 2019

Язык: Английский

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Perivascular spaces in the brain: anatomy, physiology and pathology

Nature Reviews Neurology, Год журнала: 2020, Номер 16(3), С. 137 - 153

Опубликована: Фев. 24, 2020

Язык: Английский

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Protein transmission in neurodegenerative disease

Nature Reviews Neurology, Год журнала: 2020, Номер 16(4), С. 199 - 212

Опубликована: Март 23, 2020

Язык: Английский

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Bidirectional relationship between sleep and Alzheimer’s disease: role of amyloid, tau, and other factors

Neuropsychopharmacology, Год журнала: 2019, Номер 45(1), С. 104 - 120

Опубликована: Авг. 13, 2019

Язык: Английский

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The Brain’s Glymphatic System: Current Controversies

Trends in Neurosciences, Год журнала: 2020, Номер 43(7), С. 458 - 466

Опубликована: Май 15, 2020

The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within central nervous system (CNS). Imaging studies, as well manipulations transport, point to a key role glymphatic-lymphatic clearance amyloid-β and other proteins. As such, represents new target combating neurodegenerative diseases. Not unexpectedly, introduction plumbing brain has stirred controversies. This opinion article will highlight what we know about brain's transport systems, where experimental data are lacking, still debated.

Язык: Английский

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Genomics of circadian rhythms in health and disease

Genome Medicine, Год журнала: 2019, Номер 11(1)

Опубликована: Дек. 1, 2019

Abstract Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts over myriad aspects of mammalian physiology, including the regulation sleep, metabolism, immune system. Here, we review advances in understanding genetic sleep through system, as well impact dysregulated gene expression on metabolic function. We also recent studies have begun to unravel clock’s role controlling cardiovascular nervous systems, gut microbiota, cancer, aging. Such these systems relies, part, transcriptional regulation, with evidence for genome-wide chromosome organization. These novel insights into genomic human physiology provide opportunities discovery improved treatment strategies new biological underpinnings disease.

Язык: Английский

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