Insilico Medicine, a clinical-stage biotechnology company using generative artificial intelligence (AI), has announced the publication of a new study in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. In collaboration with researchers from the University of Oslo and Akershus University Hospital, led by Dr. Sofie Lautrup and Prof. Evandro Fei Fang, the team used Insilico’s AI-driven biology platform, PandaOmics, combined with extensive experimental validation to identify potential molecular targets for Alzheimer’s disease (AD) and other neurodegenerative disorders.

The study highlights the important role of the NAD⁺–mitophagy pathway, which supports mitochondrial health and cellular quality control, in healthy brain aging and neurodegeneration. By analyzing large-scale human datasets, researchers found that disruptions in NAD⁺ metabolism and mitochondrial function occur during aging and across several neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).

Importantly, some of these molecular changes were detectable in blood samples from individuals with Alzheimer’s and Parkinson’s disease, suggesting that they could potentially serve as early blood-based biomarkers for neurodegenerative conditions.

Using PandaOmics, researchers evaluated more than 100 genes associated with NAD⁺ metabolism and mitophagy and prioritized five potential therapeutic targets for Alzheimer’s disease: ULK1, OPA1, LAMP2, MFN1, and ATP6V0E1.

The researchers then tested these targets in several preclinical models, including C. elegans, human Tau-mutant cells, and APOE4/4 iPSC-derived cortical neurons. The experiments showed that modifying these targets could influence disease-related processes. In particular, activating OPA1, a regulator of mitochondrial fusion, improved cell viability and reduced Tau phosphorylation in APOE4/4 cortical neurons. In contrast, reducing the activity of mitophagy-related genes such as MFN1 and LAMP2 increased Tau aggregation.

Overall, the findings reinforce the potential importance of mitochondrial quality control, NAD⁺ metabolism, and mitophagy in brain aging and neurodegeneration, while demonstrating how AI-driven target discovery can help identify promising avenues for future Alzheimer’s research.

Source: https://www.news-medical.net/news/20260901/AI-platform-uncovers-new-molecular-targets-for-Alzheimers-disease.aspx