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

**Authors:** Emanuel Fryk, Vagner Ramon Rodrigues Silva, Lena Strindberg, Magnus Gisslén, Henrik Zetterberg, Kaj Blennow, Per-Anders Jansson

PMC · DOI: 10.1177/13872877261421227 · Journal of Alzheimer's Disease · 2026-03-13

## TL;DR

A 6-week tadalafil treatment lowered certain blood biomarkers linked to neurodegeneration in people with type 2 diabetes.

## Contribution

This study is the first to show tadalafil's effect on plasma biomarkers of neurodegeneration in diabetic patients.

## Key findings

- Tadalafil reduced plasma amyloid-β 40 and 42 levels in participants.
- Glial fibrillary acidic protein levels were also reduced by tadalafil.
- No significant change was observed in phosphorylated tau217 or other neurodegeneration markers.

## Abstract

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.

## Linked entities

- **Chemicals:** tadalafil (PubChem CID 110635)
- **Diseases:** Alzheimer's disease (MONDO:0004975), type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Genes:** GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, PDE5A (phosphodiesterase 5A) [NCBI Gene 8654] {aka CGB-PDE, CN5A, PDE5}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** type 2 diabetes (MESH:D003924), amyloid (MESH:C000718787), AD (MESH:D000544), diabetes (MESH:D003920), neurodegeneration (MESH:D019636)
- **Chemicals:** Tadalafil (MESH:D000068581)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13022012/full.md

## References

21 references — full list in the complete paper: https://tomesphere.com/paper/PMC13022012/full.md

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Source: https://tomesphere.com/paper/PMC13022012