AI Uncovers A Cause Of Alzheimer’s Disease

A new study found that a gene recently recognised as a biomarker for Alzheimer’s disease is actually a cause of it, due to its previously unknown secondary function.  

Researchers at the University of California San Diego used Artificial Intelligence (AI) to help both unravel this mystery of Alzheimer’s disease and discover a potential treatment. 

In particular, the researchers found that Phosphoglycerate dehydrogenase deficiency (PHGDH), actually plays a causal role by disrupting gene regulation in the brain. 

About one in nine people aged 65 and older has Alzheimer’s disease, the most common cause of dementia. While some particular genes, when mutated, can lead to Alzheimer’s, that connection only accounts for a small percentage of all Alzheimer’s patients.  The vast majority of patients do not have a mutation in a known disease-causing gene; instead, they have “spontaneous” Alzheimer’s, and the causes for that are unclear.

Using AI, the team revealed that PHGDH has a hidden DNA-binding function unrelated to its known enzymatic activity.

This malfunction triggers early Alzheimer’s development, offering a new target for prevention. They also identified a small molecule, NCT-503, that blocks this harmful activity without affecting normal brain chemistry.

The key facts include:

  • Hidden Role of PHGDH: AI revealed PHGDH acts as a DNA-binding disruptor, leading to Alzheimer’s.
  • New Therapeutic Candidate: The small molecule NCT-503 blocks the harmful function without impairing normal activity.
  • Promising Results: Treated mice showed memory and anxiety improvements, suggesting clinical potential.

The San Diego team think that this opens the possibility for  a potential treatment that obstructs the gene’s moonlighting role. This new upstream target could potentially prevent the build-up of amyloid plaques, offering earlier intervention against Alzheimer’s and that further research will optimise the drug for human clinical testing.

Neuroscience   |   UCDS   |   @NeuroscienceNew   |    NIH   |   LinkedIn

Image: A.C.

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