Effect of 6-week tadalafil treatment on blood-based biomarkers of neurodegeneration: A post-hoc analysis of a randomized controlled trial

Phosphodiesterase-5 (PDE-5) inhibitors may be beneficial in Alzheimer's disease (AD). We assessed the PDE-5 inhibitor tadalafil effect on plasma biomarkers of neurodegeneration in 15 individuals with type 2 diabetes post-hoc in a randomized placebo-controlled trial (ClinicalTrials.gov: NCT02601989) at Sahlgrenska University Hospital. Tadalafil reduced plasma amyloid-β 40 and 42 but not the 42/40 ratio over a 6-week treatment period. Glial fibrillary acidic protein was reduced, but not phosphorylated tau217, neurofilament light protein or growth/differentiation factor 15. Tadalafil reduced plasma levels of biomarkers for amyloid metabolism and astroglial activation in patients with diabetes. Designated clinical trials are warranted to validate these results.