Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time

The aim od this study is to test whether metabolism of beta-amyloid and tau proteins changes in narcolepsy along with the disease course. We analyzed a population of narcoleptic drug-na < ve patients compared to a sample of healthy controls. Patients and controls underwent lumbar puncture for assessment of cerebrospinal fluid (CSF) beta-amyloid(1-42) (A beta(42)), total tau (t-tau), and phosphorylated tau (p-tau) levels. Moreover, based on the median disease duration of the whole narcolepsy group, the patients were divided into two subgroups: patients with a short disease duration (SdN, < 5 years) and patients with a long disease duration (LdN, > 5 years). We found significantly lower CSF A beta(42) levels in the whole narcolepsy group with respect to controls. Taking into account the patient subgroups, we documented reduced CSF A beta(42) levels in SdN compared to both LdN and controls. Even LdN patients showed lower CSF A beta(42) levels with respect to controls. Moreover, we documented higher CSF p-tau levels in LdN patients compared to both SdN and controls. Finally, a significant positive correlation between CSF A beta(42) levels and disease duration was evident. We hypothesize that beta-amyloid metabolism and cascade may be impaired in narcolepsy not only at the onset but also along with the disease course, although they show a compensatory profile over time. Concurrently, also CSF biomarkers indicative of neural structure (p-tau) appear to be altered in narcolepsy patients with a long disease duration. However, the mechanism underlying beta-amyloid and tau metabolism impairment in narcolepsy remains still unclear and deserves to be better elucidated.