Blood Tests Show that Obesity Rapidly Accelerates the Progression of Alzheimer’s Disease

Researchers have investigated for the first time how obesity affects blood biomarkers (BBMs) of Alzheimer’s disease. In this study, BBM levels rose up to 95% faster in people with obesity than in people without obesity, based on findings presented at the annual meeting of the Radiological Society of North America (RSNA). “This is the first time we have demonstrated the link between obesity and Alzheimer’s using blood biomarker testing,” said Dr. Cyrus Raji, lead author of the study and principal investigator at the Neuroimaging Labs Research Center at the Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis.

Long-Term Brain Imaging and Blood Data

To investigate this link, the team drew on five years of data from 407 volunteers participating in the Alzheimer’s Disease Neuroimaging Initiative, which provided both amyloid positron emission tomography (PET) scans and blood samples. PET scans are used to visualize amyloid burden in the brain, i.e., the accumulation of beta-amyloid protein in the brain in the form of amyloid plaques, a key feature of Alzheimer’s disease.

The researchers analyzed plasma samples for several BBMs associated with Alzheimer’s disease, including pTau217 levels (a biomarker used in the diagnosis and monitoring of Alzheimer’s disease), neurofilament light chain (NfL) — a protein fragment released from damaged or dying neurons — and plasma GFAP — a protein expressed mainly in astrocytes (cells that support and protect neurons in the brain and spinal cord) — using six leading commercial tests.

Link Between Body Weight and Biomarkers in the Brain

The research team used statistical methods to examine how these BBMs correlate with body mass index (BMI) and evaluated a three-way interaction between baseline obesity, time, and BBMs. They also compared and confirmed the BBM results with the results of the amyloid PET scan. When they combined the blood and imaging data, they found that at the start of the study, a higher BMI was associated with lower BBM levels and lower overall amyloid burden throughout the brain.

“We believe that the reduced BBMs in obese individuals are due to dilution by the higher blood volume,” said the study’s lead author, Dr. Soheil Mohammadi, M.P.H., a postdoctoral fellow at MIR. “If you rely solely on baseline values, you could actually come to the incorrect conclusion that people with obesity have less Alzheimer’s pathology. We need longitudinal data to fully understand how obesity affects the development of Alzheimer’s pathology.” A longitudinal study involves repeatedly collecting data from the same group over a long period of time to track changes and trends over time.

Obesity Accelerates Alzheimer’s-Related Changes

Over the years, both Alzheimer’s disease BBMs and PET scans of the brain showed a greater accumulation of Alzheimer’s-related pathologies in participants with obesity compared to those without obesity. In people with obesity, plasma pTau217 levels increased 29% to 95% faster. Obesity at the start of the study was also associated with a 24% faster increase in plasma NfL levels and a 3.7% faster increase in amyloid accumulation. Dr. Raji noted that her findings showed that blood tests are more sensitive than PET scans in detecting the influence of obesity on Alzheimer’s-related changes in the brain. “The fact that we can track the predictive influence of obesity on rising blood biomarkers more sensitively than with PET was particularly impressive to me in this study,” he said.

According to Dr. Mohammadi, the way obesity influences the progression of amyloid burden and associated changes in Alzheimer’s blood biomarkers has important implications for how clinicians assess and manage risk. “According to the 2024 Lancet Commission report, 14 modifiable risk factors account for a total of about 45% or nearly half of the risk of Alzheimer’s,” he said. “If we can reduce any of these risk factors, we can significantly reduce the number of Alzheimer’s cases or delay the onset of the disease.”

The Future of Brain Health Monitoring and Treatment

Dr. Raji believes that repeated measurements of blood biomarkers, combined with brain imaging techniques, will increasingly be used to monitor treatment strategies with anti-amyloid drugs. “This is a very exciting area of research right now, as we have drugs that can be used very effectively against obesity. This means that in future studies, we could investigate the effect of weight loss drugs on Alzheimer’s biomarkers,” he explained. “It’s wonderful that we have these blood biomarkers to track the molecular pathology of Alzheimer’s disease and MRI scans to track additional signs of brain degeneration and response to various treatments. This work is fundamental to future studies and treatment trials.”