Work

APH-1A and CDK5 Expression Correlates with Tau Hyperphosphorylation and Its Attenuation by Brahmi and Donep-M in STZ induced Alzheimer’s Disease Model

Year: 2026

Type: preprint

Abstract: 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.

Source: Research Square

DOI: 10.21203/rs.3.rs-11257702/v1

Authors: Umesh Prasad Sah Hathi, Abhishek Kumar, Jyotsna Arora, Suneel Kateriya

Institution: Jawaharlal Nehru University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Postgraduate Institute of Medical Education and Research, Chandigarh, Jawaharlal Nehru University, Indian Council of Medical Research, Advanced Instrumentation Research Facility