Suvorexant Inversely Affects Phosphorylated Tau in Human Cerebrospinal Fluid and Plasma

Suvorexant 20 mg increases plasma pT181/T181 while decreasing CSF pT181/T181 between 08:00 and 16:00 in a randomized placebo-controlled trial of 25 participants.

• Why it matters: Plasma AD biomarkers are used for screening and trial enrollment, but medication effects on their levels and proteomic context are not well defined.
• What they did: In a secondary analysis of paired CSF and plasma from 25 participants, investigators quantified plasma pT181/T181 by mass spectrometry and profiled proteomes with the SomaScan 11K assay at hours 0, 16, and 24.
• The result: At the pathway level, suvorexant increased extracellular proteins tied to translation, RNA binding, cytoskeletal organization, and endosomal sorting centrally at 16 hours and peripherally at 24 hours, while decreasing cytokine/receptor-ligand signaling and serine protease activity in plasma at 24 hours.

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