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.