Alzheimer’s disease could one day be diagnosed with a simple skin biopsy instead of invasive spinal taps or expensive brain scans.
This is the promise of scientists from the Salk Institute for Biological Studies, who have discovered stress-sensitive proteins that could act as biomarkers for the disease.
The team found a set of proteins called glycolytic enzymes that actually relocate nearby and inside mitochondria—compartments in cells where critical metabolic processes occur—when cells experience stress.
This reveals a previously unrecognized way cells adapt to damage.
This surprising “protein move-in” was seen not only in human kidney and cancer cells but also in skin biopsy-derived cells from patients with Alzheimer’s, a disease more than seven million Americans are living with.
This suggests these enzymes could serve as measurable biomarkers accessible through skin samples, according to the researchers.
More than just ‘powerhouses,’ mitochondria are response hubs that send and receive messages to regulate cellular activity. One way they send messages is by generating ‘mitochondrial reactive oxygen species’ (mtROS).
Normal mtROS signaling orchestrates many essential cellular and tissue functions, from immune responses to brain function. But if mtROS accumulate in excess, they can cause metabolic dysfunction, inflammation and aging- or disease-associated pathologies.
“Altered mitochondria and glucose metabolism and increased reactive oxygen species have all been described in Alzheimer’s disease previously, so we next looked at skin fibroblasts from Alzheimer’s disease patients and saw increased mitochondrial localization of the same enzymes here that could be reversed with antioxidants (that decrease ROS levels),” study author Gerald S. Shadel, molecular and cell biology professor at Salk, explained to Newsweek.
“Alzheimer’s disease is a brain disease involving neurons and other specialized brain cell types, so we were actually surprised to see mitochondrial and metabolic deregulation in Alzheimer’s disease skin cells.”
The findings could inform new approaches to predict or assess disorders linked to “mitochondrial dysfunction,” including Alzheimer’s, other neurodegenerative diseases and age-associated decline.
They suggest “skin biopsies could be used in some way as a diagnostic tool, most likely in combination with other tests in blood and/or CSF [cerebrospinal fluid],” according to Shadel. However, he emphasized this is still a hypothesis at this point.
“The approach has potential as it shows some systemic changes to the mitochondria as they adapt to Alzheimer’s disease. This may mean that these changes are detectable in, among other sources, skin biopsy,” neuropsychiatrist Ivan Koychev of Imperial College London, who was not involved in the present study, told Newsweek.
“This would remain to be seen in clinical studies, however. It would then need to demonstrate implementability at scale to be successful.”
Koychev noted that various minimally invasive biomarkers for neurodegeneration have been in development.
“Skin biopsy tests for Parkinson’s disease are starting to enter the market, typically in combination with smell perception tests. More broadly, blood biomarkers and digital tests of memory and thinking for Alzheimer’s and other dementias are advanced and expected to be available clinically in the short-term.”
Returning to the new findings, Julia Dudley, Head of Research at Alzheimer’s Research UK—who was also not involved in the study—told Newsweek they are “interesting” but that “it is far too early to say whether detecting these changes using skin biopsies could be used to diagnose Alzheimer’s.”
“This study used lab-grown skin cells, which could behave and appear differently from skin cells taken from a person with Alzheimer’s,” she added.
Dudley said further research needed could include seeing if the shift observed also occurs in other neurodegenerative or inflammatory conditions.
“Mitochondrial dysfunction is also seen in aging, which may begin to explain the age dependence of Alzheimer’s disease and perhaps other neurodegenerative diseases,” she said.
“Research like this is important for revealing new ways to potentially detect the presence of Alzheimer’s disease. However, there are other promising diagnostic tools in the pipeline such as using blood tests to detect the proteins linked with Alzheimer’s.”
Shadel said that the team needs to determine exactly which of the changes they identified in fibroblasts (as well as, perhaps, other changes yet to be discovered), if any, correlate with actual changes in brain cell types like neurons.
He concluded: “Our results are not informative at all in terms of treatments, but one possibility is that certain mitochondrial or metabolic changes in fibroblasts could eventually be used as a biomarker of increased risk for the disease that could be assessed before cognitive symptoms begin.”
Do you have a tip on a health story that Newsweek should be covering? Do you have a question about Alzheimer’s? Let us know via [email protected].
Reference
Esparza-Moltó, P. B., Goswami, A. V., Bozkurt, S., Münch, C., Newman, L. E., Moyzis, A. G., Rojas, G. R., Guan, D., Jones, J. R., Gage, F. H., & Shadel, G. S. (2025). ROS-dependent localization of glycolytic enzymes to mitochondria. Redox Biology, 86. https://doi.org/10.1016/j.redox.2025.103812
The post Alzheimer’s: Future Diagnoses May Come Via ‘Simple’ Skin Biopsy appeared first on Newsweek.
