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Association between hypocretin-1 and amyloid-β42 cerebrospinal fluid levels in Alzheimer's disease and healthy controls.

Abstract
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.
AuthorsDiane Slats, Jurgen A H R Claassen, Gert Jan Lammers, René J Melis, Marcel M Verbeek, Sebastiaan Overeem
JournalCurrent Alzheimer research (Curr Alzheimer Res) Vol. 9 Issue 10 Pg. 1119-25 (Dec 2012) ISSN: 1875-5828 [Electronic] United Arab Emirates
PMID22742854 (Publication Type: Journal Article)
Chemical References
  • Amyloid beta-Peptides
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
Topics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (cerebrospinal fluid)
  • Amyloid beta-Peptides (cerebrospinal fluid)
  • Circadian Rhythm
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins (cerebrospinal fluid)
  • Male
  • Middle Aged
  • Neuropeptides (cerebrospinal fluid)
  • Orexins
  • Peptide Fragments (cerebrospinal fluid)

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