APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model
Hathi UPS, Kumar A, Arora J, Kateriya S.. Research Square, 2026-10-31
Topic: Disease mechanisms in lab and animal studies
Alzheimer’s disease (AD) is a progressively characterized neurodegenerative condition marked by molecular instability, neuronal dysfunction and abnormal tau buildup. Identification of disease-associated molecular signatures that can be experimentally validated in neuronal models may provide biologically relevant biomarkers and targets for therapeutic intervention. Here, we employed an integrated transcriptomic and cellular approach to identify and validate biomarkers associated with AD pathology. Differential transcriptomic analysis of (AD versus control) samples was used to prioritize candidate genes, followed by experimental validation in a streptozotocin (STZ) induced SH-SY5Y cells. Among the selected genes, anterior pharynx defective 1A (APH-1A) and cyclin dependent kinase (CDK5) were experimentally validated and further correlated to tau pathology by quantifying phosphorylation of tau at serine 396 (p-Tau Ser396) using confocal fluorescence microscopy. Complementary atomic force microscopy (AFM) was employed to characterize STZ-associated cellular morphological alterations. STZ exposure induced an AD-like neuronal phenotype characterized by associated cellular structural abnormalities. Importantly, co-treatment with (Brahmi) attenuated STZ-associated tau Ser396 phosphorylation and improved the cellular phenotype. The effects of Brahmi were further compared with those of established anti-Alzheimer’s drugs, Donep-M (Donepezil and Memantine) together, which similarly reduced p-Tau Ser396-associated alterations. The concordance between molecular biomarker validation and imaging-based phenotypic responses warrants further investigation of underlying molecular mechanisms. Collectively, our findings establish a transcriptome-to-cellular validation framework in which APH-1A and CDK5 represent experimentally supported AD-associated biomarkers. This integrated strategy provides a foundation for connecting human AD molecular signatures with measurable neuronal phenotypes and evaluating potential therapeutic interventions.
Key findings
- Here, we employed an integrated transcriptomic and cellular approach to identify and validate biomarkers associated with AD pathology.
- Differential transcriptomic analysis of (AD versus control) samples was used to prioritize candidate genes, followed by experimental validation in a streptozotocin (STZ) induced SH-SY5Y cells.
- The effects of Brahmi were further compared with those of established anti-Alzheimer’s drugs, Donep-M (Donepezil and Memantine) together, which similarly reduced p-Tau Ser396-associated alterations.
- Collectively, our findings establish a transcriptome-to-cellular validation framework in which APH-1A and CDK5 represent experimentally supported AD-associated biomarkers.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Hathi, U. P. S., Kumar, A., Arora, J., & Kateriya, S. (2026). APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model. Research Square. https://doi.org/10.21203/rs.3.rs-11257702/v1
Vancouver
Hathi UPS, Kumar A, Arora J, Kateriya S. APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model. Research Square. 2026. doi:10.21203/rs.3.rs-11257702/v1.
BibTeX
@article{hathi2026-f749be57,
author = {Hathi, U. P. S. and Kumar, A. and Arora, J. and Kateriya, S.},
title = {{APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11257702/v1},
url = {https://doi.org/10.21203/rs.3.rs-11257702/v1}
}