A Skin Test for Alzheimer’s? New Research Offers Hope for Simpler Diagnosis
In a groundbreaking discovery that could transform how we diagnose Alzheimer’s disease, scientists at the Salk Institute have identified stress-sensitive proteins in skin cells that may serve as accessible biomarkers for the condition. Currently, diagnosing Alzheimer’s often requires invasive spinal taps or expensive brain scans, creating barriers to early detection for many patients. This new research suggests a simpler alternative might eventually be possible: a routine skin biopsy that could reveal telltale signs of the disease that affects more than seven million Americans. The research team found that certain proteins called glycolytic enzymes relocate to and inside mitochondria—the cell’s energy-producing compartments—when cells experience stress, revealing a previously unknown cellular adaptation mechanism that appears in both laboratory cells and skin cells from Alzheimer’s patients.
The discovery centers on mitochondria, which are far more than just cellular “powerhouses.” These sophisticated organelles serve as communication hubs that regulate various cellular activities by generating molecules called mitochondrial reactive oxygen species (mtROS). Under normal conditions, mtROS signaling coordinates essential functions ranging from immune responses to brain activity. However, when mtROS accumulate excessively, they can trigger metabolic dysfunction, inflammation, and pathologies associated with aging and disease. Study author Gerald S. Shadel, a molecular and cell biology professor at Salk, expressed surprise at finding these mitochondrial and metabolic irregularities in skin cells from Alzheimer’s patients, as the disease primarily affects neurons and specialized brain cells. Even more promising was the discovery that treating these cells with antioxidants could reverse these abnormal protein relocations by reducing ROS levels.
This research opens exciting possibilities for new diagnostic approaches. Rather than relying solely on cognitive assessments or expensive neuroimaging, healthcare providers might someday use skin biopsies as part of a diagnostic toolkit for Alzheimer’s and other neurodegenerative conditions. Professor Shadel suggests this approach would likely complement existing tests rather than replace them entirely. The findings are particularly significant because they indicate that Alzheimer’s disease may cause systemic changes throughout the body, not just in the brain—changes that manifest in the adaptive responses of mitochondria in various cell types, including those easily accessible through skin samples. These cellular adaptations appear to be linked to the mitochondrial dysfunction that’s increasingly recognized as a key factor in neurodegenerative diseases and age-related decline.
Expert neuropsychiatrist Ivan Koychev of Imperial College London, who wasn’t involved in the study, acknowledges the potential of this approach but emphasizes the need for additional clinical research. He notes that similar minimally invasive biomarker technologies are already being developed for other neurodegenerative conditions, such as skin biopsy tests for Parkinson’s disease that are beginning to enter the market. More broadly, blood biomarkers and digital cognitive assessments for various forms of dementia are also advancing rapidly. The development of skin-based tests would represent another valuable addition to the growing arsenal of less invasive diagnostic tools that could make early detection more accessible and affordable for patients worldwide.
Despite the excitement surrounding these findings, researchers caution that much work remains before skin biopsies could become a standard diagnostic tool for Alzheimer’s disease. Julia Dudley, Head of Research at Alzheimer’s Research UK, points out that the current study used lab-grown skin cells, which might behave differently from skin cells taken directly from individuals with Alzheimer’s. Further research is needed to determine whether the observed protein relocations are specific to Alzheimer’s or if they also occur in other neurodegenerative or inflammatory conditions. Additionally, scientists must establish whether these changes in skin cells truly correlate with changes in brain cells like neurons. The connection between mitochondrial dysfunction and aging may help explain why Alzheimer’s and other neurodegenerative diseases become more common as people get older, but confirming these relationships requires additional investigation.
While the research does not directly inform treatment approaches, it does highlight the potential for early detection before cognitive symptoms appear. Professor Shadel suggests that certain mitochondrial or metabolic changes in skin cells might eventually serve as biomarkers of increased risk for Alzheimer’s, allowing for earlier intervention. This aligns with the broader shift in Alzheimer’s research toward identifying the disease in its earliest stages, when treatments might be most effective. As this work continues alongside other promising diagnostic advances like blood tests for Alzheimer’s-related proteins, the hope is that multiple approaches will converge to create more accessible, less invasive diagnostic pathways. Such developments could dramatically improve how we identify and ultimately treat this devastating condition that affects millions of lives worldwide.
