Hypocretin-1 (orexin A) levels are normal in Huntington’s disease

Baumann, Christian R.; Hersberger, Martin; Bassetti, Claudio L.

doi:10.1007/s00415-006-0146-7

Cited by 42 publications

(20 citation statements)

References 10 publications

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“…Mean spinal CSF hypocretin-1 levels were not decreased in AD patients, corresponding to other studies [12][13][14]24].…”

Section: Hypocretin-1 Csf Levels Ad Versus Controlssupporting

confidence: 67%

“…The studies that have investigated hypocretin levels in AD patients are conflicting however. Most authors found CSF hypocretin-1 levels in AD patients comparable to controls [11][12][13][14]. One recent study in 24 advanced AD patients (braak stages 5 and 6) found lower post-mortem ventricular hypocretin-1 levels, as well as a 40% decrease in hypocretin immunoreactive neurons [15].…”

Section: Introductionmentioning

confidence: 89%

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Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Slats

Claassen²,

Lammers³

et al. 2012

CAR

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Alzheimer's disease is associated with sleep disorders. Recently, animal studies demonstrated a link between hypocretin, a sleep-regulation neurotransmitter, and AD pathology. In this study, we investigated the circadian rhythm of hypocretin-1 in Alzheimer's Disease (AD) patients and controls. Moreover, we assessed the relation between CSF hypocretin-1 and amyloid-β. A continuous CSF sampling study via indwelling intrathecal catheter was performed to collect hourly CSF samples of six patients with AD (59-85 yrs, MMSE 16-26) and six healthy volunteers (64-77 yrs). CSF hypocretin-1 and Aβ42 concentrations were determined at 8 individual time points over 24 hours. A circadian pattern was assessed by fitting a 24 hour sine curve to the hypocretin-1 data using mixed model analysis. Clinical diagnosis and Aβ42 were entered into the model as time invariant covariates to determine differences between AD and controls, and correlate Aβ42 to hypocretin-1 levels. A hypocretin-1 circadian rhythm with an amplitude of 11.5 pg/ml was found in clinical AD patients, which did not differ from the control group (7.15 pg/ml). Lower mean CSF Aβ42 levels were related to lower hypocretin-1 levels; 1.6 pg/ml hypocretin-1 per 10 pg/ml Aβ42 (p=0.03), and a higher amplitude of the hypocretin-1 circadian rhythm (0.4 pg/ml, p=0.03). CSF hypocretin-1 has a circadian rhythm for which we could show no difference between AD and controls. However, the association between mean Aβ42 levels and mean hypocretin-1 levels and amplitude may suggest a relationship between AD pathology and hypocretin disturbance, which could hold possibilities for treatment of AD related sleep disorders.

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“…Mean spinal CSF hypocretin-1 levels were not decreased in AD patients, corresponding to other studies [12][13][14]24].…”

Section: Hypocretin-1 Csf Levels Ad Versus Controlssupporting

confidence: 67%

Section: Introductionmentioning

confidence: 89%

Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Slats

Claassen²,

Lammers³

et al. 2012

CAR

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“…While to date no data on MCH levels in AD exist, literature concerning HCRT-1 is heterogenous: whereas immunoreactive neurons in postmortem hypothalami and ventricular cerebrospinal fluid (CSF)-HCRT-1 levels in AD patients were found to be reduced [25], lumbar CSF levels in vivo were unaltered [26], [27], [28]. A regulation of amyloid-beta (Aβ42) by HCRT has been concluded since the infusion of HCRT-1 in animals lead to increased levels of Aβ42 in the brain interstitial fluid.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

et al. 2013

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Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

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“…Potentially, one side of this controversy places these diseases outside the logic arrived at for sepsis, TBI and chemotherapy brain, as discussed. This impression arises from the number of reports that orexin levels in CSF samples are not significantly different in clinical cases and controls in AD [132,133] or in PD [134,135]. The alternative arguments, in favor of directly examining the orexigenic activity in the hypothalamus, and of viewing CSF levels as being a diagnostic tool to confirm severe cases rather than useful for understanding pathogenesis of AD [136,137] and PD [44,138,139], are consistent with the reasoning and methods employed in the sepsis encephalopathy and chemotherapy literature cited previously.…”

Section: Orexin In the Sleep Pathology Of Inflammatory Brain Diseasesmentioning

confidence: 99%

Inflammation-sleep interface in brain disease: TNF, insulin, orexin

Clark

Vissel

2014

J Neuroinflammation

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The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities.

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Hypocretin-1 (orexin A) levels are normal in Huntington’s disease

Cited by 42 publications

References 10 publications

Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Inflammation-sleep interface in brain disease: TNF, insulin, orexin

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Hypocretin-1 (orexin A) levels are normal in Huntington’s disease

Cited by 42 publications

References 10 publications

Association between Hypocretin-1 and Amyloid-&beta;42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Association between Hypocretin-1 and Amyloid-&beta;42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Inflammation-sleep interface in brain disease: TNF, insulin, orexin

Contact Info

Product

Resources

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Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls

Association between Hypocretin-1 and Amyloid-β42 Cerebrospinal Fluid Levels in Alzheimer’s Disease and Healthy Controls