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Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology

Published on Sep 5, 2012in Science Translational Medicine 17.16
· DOI :10.1126/scitranslmed.3004291
Jee Hoon Roh5
Estimated H-index: 5
(WashU: Washington University in St. Louis),
Yafei Huang5
Estimated H-index: 5
(WashU: Washington University in St. Louis)
+ 4 AuthorsDavid M. Holtzman42
Estimated H-index: 42
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Abstract
Aggregation of β-amyloid (Aβ) in the brain begins to occur years before the clinical onset of Alzheimer’s disease (AD). Before Aβ aggregation, concentrations of extracellular soluble Aβ in the interstitial fluid (ISF) space of the brain, which are regulated by neuronal activity and the sleep-wake cycle, correlate with the amount of Aβ deposition in the brain seen later. The amount and quality of sleep decline with normal aging and to a greater extent in AD patients. How sleep quality as well as the diurnal fluctuation in Aβ change with age and Aβ aggregation is not well understood. We report a normal sleep-wake cycle and diurnal fluctuation in ISF Aβ in the brain of the APPswe/PS1δE9 mouse model of AD before Aβ plaque formation. After plaque formation, the sleep-wake cycle markedly deteriorated and diurnal fluctuation of ISF Aβ dissipated. As in mice, diurnal fluctuation of cerebrospinal fluid Aβ in young adult humans with presenilin mutations was also markedly attenuated after Aβ plaque formation. Virtual elimination of Aβ deposits in the mouse brain by active immunization with Aβ 42 normalized the sleep-wake cycle and the diurnal fluctuation of ISF Aβ. These data suggest that Aβ aggregation disrupts the sleep-wake cycle and diurnal fluctuation of Aβ. Sleep-wake behavior and diurnal fluctuation of Aβ in the central nervous system may be functional and biochemical indicators, respectively, of Aβ-associated pathology.
  • References (49)
  • Citations (191)
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References49
Newest
Published on Aug 1, 2012in Neurobiology of Aging 4.40
Rolf Fronczek17
Estimated H-index: 17
(KNAW: Royal Netherlands Academy of Arts and Sciences),
Sarita van Geest3
Estimated H-index: 3
(KNAW: Royal Netherlands Academy of Arts and Sciences)
+ 4 AuthorsDick F. Swaab100
Estimated H-index: 100
(KNAW: Royal Netherlands Academy of Arts and Sciences)
Abstract Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic h...
Published on May 1, 2012in Cold Spring Harbor Perspectives in Medicine 5.56
Christian Haass106
Estimated H-index: 106
,
Christoph Kaether17
Estimated H-index: 17
+ 1 AuthorsSangram S. Sisodia88
Estimated H-index: 88
Accumulations of insoluble deposits of amyloid β-peptide are major pathological hallmarks of Alzheimer disease. Amyloid β-peptide is derived by sequential proteolytic processing from a large type I trans-membrane protein, the β-amyloid precursor protein. The proteolytic enzymes involved in its processing are named secretases. β- and γ-secretase liberate by sequential cleavage the neurotoxic amyloid β-peptide, whereas α-secretase prevents its generation by cleaving within the middle of the amyloi...
Published on Mar 28, 2012in The Journal of Neuroscience 6.07
Adam W. Bero6
Estimated H-index: 6
,
Adam Q. Bauer16
Estimated H-index: 16
+ 5 AuthorsDavid M. Holtzman118
Estimated H-index: 118
(WashU: Washington University in St. Louis)
Brain region-specific deposition of extracellular amyloid plaques principally composed of aggregated amyloid-β (Aβ) peptide is a pathological signature of Alzheimer9s disease (AD). Recent human neuroimaging data suggest that resting-state functional connectivity strength is reduced in patients with AD, cognitively normal elderly harboring elevated amyloid burden, and in advanced aging. Interestingly, there exists a striking spatial correlation between functional connectivity strength in cognitiv...
Published on Jan 1, 2012in JAMA Neurology 12.32
Yafei Huang5
Estimated H-index: 5
,
Rachel Potter3
Estimated H-index: 3
+ 8 AuthorsStephen P. Duntley22
Estimated H-index: 22
Background The amyloid hypothesis predicts that increased production or decreased clearance of β-amyloid (Aβ) leads to amyloidosis, which ultimately culminates in Alzheimer disease (AD). Objective To investigate whether dynamic changes in Aβ levels in the human central nervous system may be altered by aging or by the pathology of AD and thus contribute to the risk of AD. Design Repeated-measures case-control study. Setting Washington University School of Medicine in St Louis, Missouri. Participa...
Published on Dec 21, 2011in Science Translational Medicine 17.16
David M. Holtzman118
Estimated H-index: 118
,
Alison Goate112
Estimated H-index: 112
+ 1 AuthorsReisa A. Sperling87
Estimated H-index: 87
Alzheimer’s disease (AD) is the most common cause of dementia and will lead to a worldwide public health crisis if it continues unchecked. Despite tremendous advances in our scientific understanding of AD, we still do not have effective ways to delay, prevent, or slow this disease. At the 2011 Abelson meeting, a diverse group of scientists discussed current challenges in the AD field and made recommendations in the areas of genetics, clinical trials, protein aggregation, and the cell biology of ...
Published on Nov 2, 2011in The Journal of Neuroscience 6.07
Soyon Hong17
Estimated H-index: 17
,
Omar Quintero-Monzon1
Estimated H-index: 1
+ 6 AuthorsDennis J. Selkoe161
Estimated H-index: 161
Growing evidence supports the hypothesis that soluble, diffusible forms of the amyloid β-peptide (Aβ) are pathogenically important in Alzheimer's disease (AD) and thus have both diagnostic and therapeutic salience. To learn more about the dynamics of soluble Aβ economy in vivo , we used microdialysis to sample the brain interstitial fluid (ISF), which contains the most soluble Aβ species in brain at steady state, in >40 wake, behaving APP transgenic mice before and during the process of Aβ plaqu...
Published on Nov 1, 2011in Nature Neuroscience 21.13
Stephanie Maret2
Estimated H-index: 2
(UW: University of Wisconsin-Madison),
Ugo Faraguna15
Estimated H-index: 15
+ 2 AuthorsGiulio Tononi96
Estimated H-index: 96
(UW: University of Wisconsin-Madison)
Using two-photon microscopy in mice, the authors find that the number of cortical spines increases in adolescent mice while they are awake and decreases while they are asleep.
Published on Nov 1, 2011in Annals of Neurology 9.50
Gregory J. Tranah28
Estimated H-index: 28
(UCSF: University of California, San Francisco),
Terri Blackwell45
Estimated H-index: 45
(UCSF: University of California, San Francisco)
+ 8 AuthorsSteve Cummings152
Estimated H-index: 152
(UCSF: University of California, San Francisco)
Objective—Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).
Published on Jun 1, 2011in Nature Neuroscience 21.13
Adam W. Bero6
Estimated H-index: 6
(WashU: Washington University in St. Louis),
Ping Yan15
Estimated H-index: 15
(WashU: Washington University in St. Louis)
+ 5 AuthorsDavid M. Holtzman2
Estimated H-index: 2
(WashU: Washington University in St. Louis)
Using a mouse model of Alzheimer's disease and in vivo microdialysis, this study shows that neuronal activity drives the level of interstitial fluid amyloid-β and subsequent amyloid-β plaque deposition.
Published on May 1, 2011in Alzheimers & Dementia 14.42
Reisa A. Sperling87
Estimated H-index: 87
(Brigham and Women's Hospital),
Paul S. Aisen82
Estimated H-index: 82
(UCSD: University of California, San Diego)
+ 18 AuthorsThomas J. Montine88
Estimated H-index: 88
(UW: University of Washington)
Abstract The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiolo...
Cited By191
Newest
Published on Mar 14, 2019in Scientific Reports 4.01
Sidra Tabassum1
Estimated H-index: 1
(SCNU: South China Normal University),
Afzal Misrani1
Estimated H-index: 1
(SCNU: South China Normal University)
+ 3 AuthorsCheng Long3
Estimated H-index: 3
(SCNU: South China Normal University)
Sleep deprivation (SD) is the hallmark of modern society and may increase risk of Alzheimer’s disease (AD). However, it is unclear how SD facilitates early cognitive impairments observed in AD models, as the underlying molecular mechanism is largely unknown. Here, we aim to investigate SD-induced cellular and molecular alterations in hippocampus of young APP/PS1 mice and whether jujuboside A (JuA) treatment could negate these alterations. Our results reveal that although SD causes spatial memory...
Published on Dec 1, 2019in Scientific Reports 4.01
Ksenia V. Kastanenka7
Estimated H-index: 7
(Harvard University),
María Calvo-Rodríguez (Harvard University)+ 12 AuthorsJonathan M. Hawkes4
Estimated H-index: 4
(Harvard University)
Neuronal activity patterns are disrupted in neurodegenerative disorders, including Alzheimer’s disease (AD). One example is disruption of corticothalamic slow oscillations responsible for sleep-dependent memory consolidation. Slow waves are periodic oscillations in neuronal activity occurring at frequencies of <1 Hz. The power, but not the frequency of slow oscillations is altered in a mouse model of AD. Optogenetic rescue of slow oscillations by increasing activity in cortical pyramidal neurons...
Published in Sleep and Breathing 2.33
Michelangelo Maestri18
Estimated H-index: 18
(UniPi: University of Pisa),
Andrea Romigi22
Estimated H-index: 22
+ -3 AuthorsEnrica Bonanni18
Estimated H-index: 18
(UniPi: University of Pisa)
Excessive daytime sleepiness (EDS) and fatigue are some of the most frequent symptoms in neurological diseases and could impact on quality of life by increasing the risk of accidents and generally affecting daily life activities. In this review, we will examine the variety of causes responsible for EDS in neurological diseases, including nocturnal sleep alterations, CNS pathological abnormalities with alterations in arousal and/or REM regulation systems, circadian rhythms disorders, drugs, and c...
Published on Jun 17, 2019in The Journal of Neuroscience 6.07
Joseph R. Winer4
Estimated H-index: 4
(University of California, Berkeley),
Bryce A. Mander12
Estimated H-index: 12
(University of California, Berkeley)
+ 6 AuthorsMatthew P. Walker51
Estimated H-index: 51
(HWNI: Helen Wills Neuroscience Institute)
Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer9s disease (AD): tau and β-amyloid (Aβ). Here we combined positron emission tomography measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow ...
Published on Jun 1, 2019in Trends in Molecular Medicine 11.03
Kelly H. Forest1
Estimated H-index: 1
(U.H.: University of Hawaii at Manoa),
Robert A. Nichols20
Estimated H-index: 20
(U.H.: University of Hawaii at Manoa)
Alzheimer’s disease (AD) is a relentlessly progressive neurodegenerative disease, currently incurable, which presents one of the largest unmet needs in medicine. AD is histologically characterized by the accumulation of extracellular amyloid-beta (Aβ), evident as senile plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. However, the levels of diffusible extracellular Aβ, a neuropeptide largely present in oligomeric form, rise by orders of magnitude many years ...
Published on May 1, 2019in Neurologic Clinics 2.80
Marc D. Ruben6
Estimated H-index: 6
,
John B. Hogenesch63
Estimated H-index: 63
,
David F. Smith16
Estimated H-index: 16
Published on Jul 3, 2019in Neurotherapeutics 5.55
J. C. Ryu (OSU: Ohio State University), E. R. Zimmer (PUCRS: Pontifícia Universidade Católica do Rio Grande do Sul)+ 1 AuthorsS. O. Yoon (OSU: Ohio State University)
Alzheimer’s disease (AD) is an irreversible, progressive disease that slowly destroys cognitive function, such as thinking, remembering, and reasoning, to a level that one cannot carry out a daily living. As people live longer, the risk of developing AD has increased to 1 in 10 among people who are older than 65 and to almost 1 in 2 among those who are older than 85 according to a 2019 Alzheimer’s Association report. As a most common cause of dementia, AD accounts for 60–80% of all dementia case...
Published in Neurotherapeutics 5.55
Thierno M. Bah1
Estimated H-index: 1
(OHSU: Oregon Health & Science University),
James R. Goodman4
Estimated H-index: 4
(OHSU: Oregon Health & Science University),
Jeffrey J. Iliff1
Estimated H-index: 1
(OHSU: Oregon Health & Science University)
Sleep is a behavioral phenomenon conserved among mammals and some invertebrates, yet the biological functions of sleep are still being elucidated. In humans, sleep time becomes shorter, more fragmented, and of poorer quality with advancing age. Epidemiologically, the development of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease is associated with pronounced sleep disruption, whereas emerging mechanistic studies suggest that sleep disruption may be causally lin...
Published on Jun 24, 2019in Frontiers in Aging Neuroscience 3.63
G Edwards1
Estimated H-index: 1
(University of Texas Health Science Center at Houston),
Nazaret Gamez (UMA: University of Málaga)+ 2 AuthorsInes Moreno-Gonzalez14
Estimated H-index: 14
(UMA: University of Málaga)
Since first described in the early 1900s, Alzheimer’s disease (AD) has risen exponentially in prevalence and concern. Research still drives to understand the etiology and pathogenesis of this disease and what risk factors can attribute to AD. With a majority of AD cases being of sporadic origin, the increasing exponential growth of an aged population and a lack of treatment, it is imperative to discover an easy accessible preventative method for AD. Some risk factors can increase the propensity ...