A Promising Study Suggests a Blood Test Could Spot Alzheimer’s Early in Progression
Could support earlier interventions as new therapies, including anti-amyloid drugs, show greater benefit when started sooner
Researchers at the Icahn School of Medicine at Mount Sinai have made a discovery that opens the door to a potential future in which a simple minimally invasive blood test could help identify adults in late midlife who are at higher risk of eventual cognitive decline, enabling earlier lifestyle interventions or monitoring well before dementia symptoms appear.
The discovery, published today in BMC Neurology, resulted from the first comprehensive analysis of changes in mitochondrial DNA (mtDNA) found in the blood of patients in late midlife, which the researchers defined as ages 40 to 65. The researchers identified specific changes, or variants, that were related to declines in cognition.
Mitochondria are the tiny powerhouses that produce energy inside our cells. They are critical to a healthy brain, an organ with enormous energy demands and poor storage capacity. Unlike nuclear DNA, the most well-known kind, mitochondria carry their own small set of genetic material called mitochondrial DNA. When damaged, mtDNA cannot repair itself as effectively as nuclear DNA.
“And thus, we may be getting close to a blood test foreshadowing cognitive decline and even Alzheimer’s,” said first author Diddier Prada, MD, PhD, Assistant Professor of Population Health Science and Policy, and Environmental Medicine, at the Icahn School of Medicine at Mount Sinai. Dr. Prada initiated the research through the School’s Institute for Health Equity Research. The study includes a balanced representation of Black and white participants, addressing gaps in the representation of diverse populations.
“A blood biomarker could eventually support earlier interventions—for example, lifestyle changes that include modifications to exercise and diet and reducing inflammation. Earlier interventions align with what we know about the efficacy of newer Alzheimer’s drugs, which work best when started in the earliest stages,” said Dr. Prada.
Current population projections suggest that the burden of Alzheimer’s disease in those 65 years or older will rise to nearly 14 million people by 2060. Dr. Prada and his research colleagues, struck by the growing public health crisis of Alzheimer’s disease and other manifestations of cognitive decline, set out to find answers to the biological drivers taking place in those who had not yet reached 65.
“Your cognitive abilities at midlife reflect one of the strongest predictors of whether you will develop dementia, yet we still haven’t connected the dots. Importantly, emerging data suggest a strong link between our mitochondria and cognitive decline. However, we don’t have a reliable and consistent blood test to evaluate mitochondrial changes in midlife,” Dr. Prada said. “Blood tests to detect these mutations have not yielded consistent results related to cognitive decline. That gap is what drove us. No one had done a comprehensive analysis like this before.”
To perform the first comprehensive analysis of mitochondria in blood, Dr. Prada’s team used high-depth sequencing with extensive quality controls to detect the most subtle heteroplasmic change, which would detect the presence of more than one type of mtDNA within the same cell or individual—across functional mtDNA regions and individual genes.
Study Highlights:
- Variants in the mitochondrial gene NADH dehydrogenase subunit 1 (ND1), which helps the cell produce energy, were associated with lower baseline cognitive scores of up to 2.6-points. This suggests that problems in how cells synthesize energy may influence cognitive function.
- Variants in mitochondrial genes, such as ND6 and ATP8, were associated with a reduction of 1.2 to 1.4 points in task performance and higher-order thinking over time. This seemingly small reduction is quite important because it may represent an early sign of neurodegeneration that can progressively impair daily functioning in the future.
- A higher total number of mtDNA variants was linked to worse word retrieval. Variants in the region that controls mtDNA showed the strongest effect, with each additional variant associated with a 0.2-point decline in verbal fluency. This finding is important because word retrieval requires complex coordination among different brain areas involved in language, memory, and thinking.
Although these findings are preliminary and based on a modest sample size of 197 adults, larger longitudinal studies are already underway. Nevertheless, this research offers an important early glimpse into a future where Alzheimer’s disease and other dementias could be detected much earlier. It also strengthens the case for midlife lifestyle interventions and helps lay the foundation for incorporating mitochondrial biomarkers into clinical prevention trials—potentially reducing the growing public health burden of Alzheimer’s disease and age-related cognitive decline.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 4705 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 90th percentile of U.S. private medical schools in Sponsored Programs Direct Expenditures per Principal Investigator, according to the Association of American Medical Colleges. More than 6,900 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 10 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2025-2026.
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