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Pyk2 plays a critical role in synaptic dysfunction during the early stages of Alzheimer’s disease
Quentin Rodriguez, Floriane Payet, Karina Vargas-Baron, Eve Borel, Fabien Lanté, Sylvie Boisseau, Béatrice Blot, Jean‐Antoine Girault et al.. Molecular Neurodegeneration Advances, 2026-03-07
Topic: Brain proteins, microglia and lab models
The locus of the gene PTK2B encoding the tyrosine kinase Pyk2 has been associated with the risk of late-onset Alzheimer’s disease, the predominant form of dementia. Pyk2 is primarily expressed in neurons where it is involved in excitatory neurotransmission and synaptic functions. Although previous studies have implicated Pyk2 in amyloid-β and Tau pathologies of Alzheimer’s disease, its exact role remains unresolved, with evidence showing both detrimental and protective effects in mouse models. Here, we investigate the role of Pyk2 in hippocampal hyperactivity, Tau synaptic localization and synaptic loss associated with Alzheimer’s disease-related alterations occurring in the early stages of the disease. Pyk2’s involvement in amyloid-β oligomer-induced hippocampal neuronal hyperactivity was investigated using whole-cell patch clamp in hippocampal slices from WT and Pyk2 KO mice. Various Pyk2 mutants were overexpressed in cultured cortical neurons to study Pyk2’s role in synaptic loss. Pyk2 and Tau interaction was assessed with bimolecular fluorescence complementation assays in cultured neurons and co-immunoprecipitation in mouse cortex. To evaluate the impact of Pyk2 on Tau expression in synapses, cellular fractionation was performed on hippocampi from WT and Pyk2 KO mice. Genetic deletion of Pyk2 prevented amyloid-β oligomer-induced hippocampal neuronal hyperactivity and synaptic loss. Overexpression of Pyk2 in neurons decreased dendritic spine density independently of its autophosphorylation or kinase activity, but through its proline-rich motif 1. Furthermore, Pyk2 interacted with Tau in synapses, while Pyk2 deletion decreased Tau synaptic localization in the hippocampus. Pyk2 contributes to hippocampal neuronal hyperactivity and synaptic loss, two early events in Alzheimer’s disease pathogenesis. It is also involved in Tau synaptic localization, a process known to be detrimental in Alzheimer’s disease. These findings highlight Pyk2 as a critical player in Alzheimer’s disease pathophysiology and suggest its potential as a promising therapeutic target for early intervention.
Key findings
- The locus of the gene PTK2B encoding the tyrosine kinase Pyk2 has been associated with the risk of late-onset Alzheimer’s disease, the predominant form of dementia.
- Here, we investigate the role of Pyk2 in hippocampal hyperactivity, Tau synaptic localization and synaptic loss associated with Alzheimer’s disease-related alterations occurring in the early stages of the disease.
- These findings highlight Pyk2 as a critical player in Alzheimer’s disease pathophysiology and suggest its potential as a promising therapeutic target for early intervention.
Why it matters
In mouse and cell experiments, deleting the gene for the protein Pyk2 prevented amyloid-beta oligomer-induced hippocampal neuronal hyperactivity and synaptic loss, pointing to Pyk2 as a possible target in early Alzheimer's disease. These are laboratory findings, not yet evidence that targeting Pyk2 helps people.
Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular Neurodegeneration Advances) |
| Journal's citation record | 0 / 4 | Molecular Neurodegeneration Advances: journal h-index 3 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Alain Buisson: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 32 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s44477-026-00021-4
- Original source →
- Free full text: Molecular Neurodegeneration Advances →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Rodriguez, Q., Payet, F., Vargas-Baron, K., Borel, E., Lanté, F., Boisseau, S., et al. (2026). Pyk2 plays a critical role in synaptic dysfunction during the early stages of Alzheimer’s disease. Molecular Neurodegeneration Advances. https://doi.org/10.1186/s44477-026-00021-4
Vancouver
Rodriguez Q, Payet F, Vargas-Baron K, Borel E, Lanté F, Boisseau S, et al. Pyk2 plays a critical role in synaptic dysfunction during the early stages of Alzheimer’s disease. Molecular Neurodegeneration Advances. 2026. doi:10.1186/s44477-026-00021-4.
BibTeX
@article{rodriguez2026-0f626c1d,
author = {Rodriguez, Quentin and Payet, Floriane and Vargas-Baron, Karina and Borel, Eve and Lanté, Fabien and Boisseau, Sylvie and Blot, Béatrice and Girault, Jean‐Antoine and others},
title = {{Pyk2 plays a critical role in synaptic dysfunction during the early stages of Alzheimer’s disease}},
journal = {Molecular Neurodegeneration Advances},
year = {2026},
doi = {10.1186/s44477-026-00021-4},
url = {https://doi.org/10.1186/s44477-026-00021-4}
}
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