Obesity raises risk of Alzheimer’s disease blood markers

Results from the first-ever study measuring the impact of obesity on Alzheimer’s disease blood biomarkers (BBMs) reveal that BBM values rose up to 95% faster in obese individuals compared to those of healthy weight.

To investigate this condition, scientists reviewed data from the Alzheimer’s Disease Neuroimaging Initiative, which tracked 407 participants over five years, including amyloid PET scans and blood samples.

PET scans demonstrate the brain’s amyloid burden, referring to how beta-amyloid protein accumulates in the brain in the form of amyloid plaques, which is a typical sign of Alzheimer’s disease.

“This is the first time we’ve shown the relationship between obesity and Alzheimer’s disease as measured by blood biomarker tests,” says study senior author Cyrus Raji, M.D., Ph.D., principal investigator in the Neuroimaging Labs Research Center at Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri, US.

Importance of longitudinal research

Using six leading commercial tests, the team tested plasma samples for BBMs associated with Alzheimer’s disease, which included:

• Levels of pTau217 (a biomarker used in the diagnosis and monitoring of Alzheimer’s disease).
• Neurofilament light chain (or NfL, a protein fragment released from damaged or dying neurons).
• Plasma GFAP (a protein expressed primarily in astrocytes cells that support and protect neurons in the brain and spinal cord).

The researchers performed statistical analysis to assess the association between the BBMs and body mass index (BMI) and the three-way interaction between baseline obesity, time, and BBMs. 

The researchers also validated the BBMs against the amyloid PET scans.

Analysis of the BBMs and PET scan data demonstrated that at baseline, BMI was associated with lower BBMs and reduced whole-brain amyloid burden.

“We believe the reduced BBMs in obese individuals was due to dilution from the higher blood volume,” says study lead author Soheil Mohammadi, M.D., M.P.H., postdoctoral research associate at MIR.

“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’s disease. We need the longitudinal data to fully understand how obesity impacts the development of Alzheimer’s disease pathology.”

Developments over time

Over time, Alzheimer’s disease BBMs and brain PET scans showed an increased burden of Alzheimer’s disease pathology in individuals with obesity compared with non-obese individuals.

Comparatively, participants with obesity had a 29–95% faster rate of increase in plasma pTau217 ratio levels. Baseline obesity led to a 24% faster rate of increase in plasma NfL and a 3.7% faster rate of increase in amyloid accumulation.

Raji notes that the analysis demonstrated how the blood tests were more sensitive than the PET scans in capturing the impact of obesity on Alzheimer’s disease pathology.

“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,” he notes.

Mohammadi underscores that obesity’s amyloid burden and corresponding changes in blood biomarkers for Alzheimer’s disease should be essential considerations for clinical practice.

“According to the 2024 report of the Lancet Commission, 14 modifiable risk factors total approximately 45%, or close to half, of the risk for Alzheimer’s disease,” he highlights. “If we can reduce any of those risk factors, we can significantly reduce Alzheimer’s cases or lengthen the amount of time until the onset of the disease.”

Implications for brain therapies

Raji believes longitudinal assessments with blood biomarkers and brain health imaging will become the norm for monitoring treatments that involve anti-amyloid drugs.

“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’s disease biomarkers in future studies,” he comments.

“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.”

The researchers presented their findings at the recent annual meeting of the Radiological Society of North America (Nov 30 to Dec 4).

Among other Alzheimer’s disease intervention studies, international scientists in a recent paper suggest that boosting NAD+ may help protect the brain from the degenerative effects of the condition. As a vital metabolite in energy metabolism and neuronal resilience, NAD+ in the body naturally declines with age, especially in neurodegenerative diseases.

Earlier this month, Japanese scientists also uncovered that oral arginine, a naturally occurring amino acid, may significantly reduce a precursor to Alzheimer’s disease. In their experiment involving mice and fruit flies, arginine lowered amyloid β plaque formation.

Another report from the UK supports that omega-3 fatty acids may help protect women against Alzheimer’s disease, potentially more than men. Women with the disease exhibited a noticeable loss of unsaturated fats in their blood samples, such as those containing omega fatty acids.

Meanwhile, individuals with the highest genetic risk for Alzheimer’s disease tend to benefit more from following a Mediterranean-style diet, according to research in Nature Medicine.