Description:
<jats:title>Summary</jats:title><jats:p>Narcolepsy is characterized by hypocretin deficiency due to the loss of hypothalamic orexinergic neurons, and is associated with both the human leucocyte antigen <jats:styled-content style="fixed-case">DQB</jats:styled-content>1*06:02 and the <jats:styled-content style="fixed-case">T</jats:styled-content> cell receptor polymorphism. The above relationship suggests autoimmune/inflammatory processes underlying the loss of orexinergic neurons in narcolepsy. To test the autoimmune/inflammatory hypothesis by means of cerebrospinal fluid (<jats:styled-content style="fixed-case">CSF</jats:styled-content>) levels of beta‐amyloid<jats:sub>1–42</jats:sub> and/or total tau proteins in a sample of narcoleptic patients, we analysed 16 narcoleptic patients and 16 healthy controls. Beta‐amyloid<jats:sub>1–42</jats:sub> <jats:styled-content style="fixed-case">CSF</jats:styled-content> levels were significantly lower in narcoleptic patients compared with healthy controls. We also documented pathologically low levels of <jats:styled-content style="fixed-case">CSF</jats:styled-content> beta‐amyloid<jats:sub>1–42</jats:sub> (<500 pg mL<jats:sup>−1</jats:sup>) in six of 16 narcoleptic patients (37.5%). We hypothesize that the significant decrease of the <jats:styled-content style="fixed-case">CSF</jats:styled-content> beta‐amyloid<jats:sub>1–42</jats:sub> levels in narcoleptic patients may support both the inflammatory/autoimmune hypothesis as the basis of the pathogenesis of narcolepsy and the prevalence of an ‘amyloidogenic’ pathway caused by the deficiency of the alpha‐secretases enzymes.</jats:p>