Obesity Linked to Faster Alzheimer Disease Progression in Longitudinal Blood Biomarker Analysis

Findings from a first-of-its kind study suggest that obesity may accelerate Alzheimer disease (AD)–related changes, based on a long-term analysis of blood-based biomarkers (BBM).

In a 5-year dataset from 407 participants in the Alzheimer’s Disease Neuroimaging Initiative, researchers found that AD BBM values rose 29% to 95% faster in individuals with obesity than in those without obesity. The investigators also observed a 3.7% faster rate of amyloid accumulation on PET and a 24% faster rise in plasma NfL among participants with obesity.

"This is the first time we've shown the relationship between obesity and [Alzheimer] disease as measured by blood biomarker tests," Cyrus Raji, MD, PhD, senior author and principal investigator in the Neuroimaging Labs Research Center at Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine,said in a statement.

Results of the new analysis were presented at the Radiological Society of North America (RSNA) annual meeting, November 30 - December 4, in Chicago.

Short-Term Data Could Be Misleading

The study used amyloid PET imaging and longitudinal plasma sampling to evaluate pTau217, neurofilament light chain (NfL), and plasma GFAP using 6 standard commercial assays. Participants contributed repeated measurements over 5 years, allowing Raji and colleagues to assess how baseline obesity interacted with time and biomarker trajectories. Investigators also validated BBM trends against amyloid PET results.

Initial cross-sectional analysis showed that higher body mass index (BMI) correlated with lower BBM values and reduced whole-brain amyloid burden. "We believe the reduced BBMs in obese individuals was due to dilution from the higher blood volume," study lead author Soheil Mohammadi, MD, MPH, a postdoctoral research associate at MIR, said. "In fact, by relying on the baseline measurements, you could be fooled into thinking that the people with obesity had a lower pathology of [Alzheimer] disease. We need the longitudinal data to fully understand the how obesity impacts the development of [AD] pathology."

The researchers reported that the biomarker trajectories diverged over the 5-year study period, with a rise between approximately one-third and nearly 100% steeper in plasma pTau217 ratio levels among participants with obestiy compared with non-obese participants. Longitudinal increases in NfL and GFAP aligned with greater PET-based amyloid burden, according to the investgiators.

Differences in the sensitivity for disease burden between the 2 modalities were a surprise. "The fact that we can track the predictive influence of obesity on rising blood biomarkers more sensitively than PET is what astonished me in this study," PI Raji said.

Obesity as Modifiable Risk Factor for Dementia

Mohammadi added that the findings reinforce the relevance of weight-related risk factors in clinical decision-making. "According to the 2024 report of the Lancet Commission,² 14 modifiable risk factors total approximately 45%, or close to half, of the risk for [Alzheimer] disease," he said. "If we can reduce any of those risk factors, we can significantly reduce [Alzheimer] cases or lengthen the amount of time until the onset of the disease."

Serial BBM testing, combined with imaging, may soon guide decisions around anti-amyloid therapies, Raji predicted. "This is such profound science to follow right now because we have drugs that can treat obesity quite powerfully, which means we could track the effect of weight loss drugs on [Alzheimer] biomarkers in future studies," he said. "It's marvelous that we have these blood biomarkers to track the molecular pathology of Alzheimer's disease, and MRI scans to track additional evidence of brain degeneration and response to various treatments. This work is foundational for future studies and treatment trials."

References

1. Blood test shows obesity speeds Alzheimer's development. News release. Radiological Society of North America. December 2, 2025. Accessed December 2, 2025. https://prnmedia.prnewswire.com/news-releases/blood-test-shows-obesity-speeds-alzheimers-development-302627268.html
2. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024;404(10452). doi:10.1016/S0140-6736(24)01296-0