Hypocretin in cerebrospinal fluid is positively correlated with Tau and pTau

• Hypocretin concentrations in CSF do not differ between patients with Alzheimer's disease and major depression.
• Hypocretin concentrations in CSF are related to Tau and phosphorylated Tau (pTau) in CSF.
• Independent from diagnoses, hypocretin might be related to the regulation of Tau protein.

It has been suggested that sleep–wake regulation as well as hypocretins play a role in the pathophysiology of Alzheimer's disease. We analyzed Aβ40, Aβ42, Tau protein, phosphorylated Tau (pTau) protein as well as hypocretin-1 concentrations in the CSF of a detection sample of 10 patients with Alzheimer's disease (AD) as well as 10 age- and gender-matched patients with major depression as a comparison group of different pathology. In order to replicate the findings, we used a confirmation sample of 17 AD patients and 8 patients with major depression. We found hypocretin-1 concentrations in CSF not to differ between patients with depression and AD. However, hypocretin-1 was significantly related to Tau (r = 0.463, p < 0.001) and pTau (r = 0.630, p < 0.0001). These effects were more pronounced in depressed patients when compared to AD patients. We conclude that hypocretin-1 may play a role in the metabolism of Tau proteins across different diagnostic entities including AD. It has to be determined whether there is a causal relationship between hypocretin-1 and Tau as well as pTau.