A new study reshapes our understanding of Alzheimer’s disease. Researchers identify the PHGDH gene not just as a marker, but as a driver of brain changes linked to Alzheimer’s. They also spotlight a candidate drug-like compound that could slow the disease in its earliest stages. The finding holds particular relevance for aging societies like Thailand, where dementia care poses rising health and social challenges.
Globally, Alzheimer’s is the most common form of dementia, affecting roughly one in nine people aged 65 and older. In Thailand, the rapidly growing elderly population brings heightened concerns about cognitive decline and dementia care. While rare genetic mutations are known to cause some cases, most Alzheimer’s cases arise spontaneously. This research offers fresh scientific insight and potential hope for families and health systems facing dementia.
The study, featured in Cell on April 23, 2025, comes from a team at a leading U.S. university. Using artificial intelligence and advanced lab models, the researchers linked increased PHGDH expression to Alzheimer’s progression. They found that PHGDH does more than support serine production; a hidden DNA-binding-like domain suggests PHGDH also acts as a regulator of gene activity in brain cells. This dual role may spark early brain changes that set the disease in motion.
Experiments in mice and human brain organoids showed that higher PHGDH levels accelerate disease, while lower levels slow it. This positions PHGDH as an active initiator of spontaneous Alzheimer’s, not merely an associated factor. Such insight could shift future research and treatment strategies toward the PHGDH pathway.
Crucially, the researchers identified a compound called NCT-503 that selectively blocks PHGDH’s regulatory activity without disrupting its essential enzyme function. NCT-503 can cross the blood-brain barrier and does not impede serine production, addressing safety concerns. In preclinical tests, treated mice demonstrated improvements in memory and reduced anxiety-like symptoms. This points to a potential new class of brain-penetrant therapies.
Most current Alzheimer’s drugs target amyloid plaques that accumulate later in the disease. The new PHGDH pathway appears upstream, offering the possibility of preventing or slowing plaque formation before symptoms intensify. This upstream approach could provide valuable time for patients to retain function.
Acknowledging limitations is important. There are no perfect animal models for spontaneous Alzheimer’s, and human trials are needed before any new treatments become available. Nonetheless, the discovery of PHGDH’s dual roles opens the door to novel small-molecule therapies that could eventually be taken orally, reducing the need for hospital-based infusions.
For Thailand, the implications are especially meaningful. The country’s aging society heightens dementia risk for families and public health systems. Data from Thailand’s Ministry of Public Health shows dementia prevalence is expected to rise in the coming decades, underscoring the importance of early diagnostic tools and accessible treatments. Blood-based biomarkers targeting PHGDH could enable early identification of at-risk individuals, while orally administered therapies could reach people in rural areas more easily than infusion-based options.
Memory loss touches deeply held Thai values about family and community. This situation challenges personal dignity and harmony but also aligns with a desire to support elders in staying active and engaged. As medical science advances, maintaining cognitive health longer could help aging Thais remain active contributors within families and communities, including rural elders who are often respected as knowledge-keepers but may face isolation if dementia develops.
Looking ahead, the research suggests a future where Alzheimer’s could be detected and treated earlier, preserving independence and dignity. If future clinical studies confirm safety and efficacy in people, Thailand’s healthcare system—from regional clinics to major universities—should prepare to deploy new diagnostics and therapies. Collaboration among policymakers, clinicians, and public health educators will be essential to raise awareness, promote regular screening for memory health, and support families navigating care.
For readers concerned about memory health, staying informed about emerging Alzheimer’s advances is prudent. Seek regular medical advice for elderly relatives and watch for new diagnostic tests or therapies as discoveries move toward clinical use. Supporting local dementia research and public health initiatives remains crucial, alongside compassionate family support.
Notes:
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