Research links hidden visceral fat to abnormal proteins in the brain – predicts Alzheimer’s disease decades before diagnosis.
Researchers from Washington University School of Medicine have revealed a significant link between visceral fat – fat stored around internal organs – and the accumulation of amyloid plaques and tau tangles in the brain. These proteins are well-established hallmarks of Alzheimer’s disease, and the study, which was presented at the Radiological Society of North America’s annual meeting earlier this month, suggests that targeting visceral fat in midlife could offer a preventive strategy against the condition.
Longevity.Technology: Despite decades of research and investment, therapies for Alzheimer’s disease have achieved limited success; those with benefits are most effective when the condition is caught early, such as aducanumab and lecanemab. Grabbing headlines, both these drugs target amyloid-beta plaques in the brain, and have emerged as promising disease-modifying therapies, aiming to slow disease progression rather than merely addressing symptoms, with their effectiveness being most pronounced when administered in the early stages. With Alzheimer’s already affecting 6.9 million Americans – a number projected to double by 2050 – early detection is crucial to slow progression and mitigate its growing burden on individuals and healthcare systems [1]. Understanding modifiable risk factors, such as obesity, may provide a new avenue for intervention.
A focus on midlife indicators
The team from Mallinckrodt Institute of Radiology (MIR) at WashU Medicine in St Louis, Missouri, examined 80 cognitively normal adults with an average age of 49.4 years, using advanced imaging techniques and metabolic assessments to analyze the relationship between various fat types, metabolic factors and Alzheimer’s biomarkers. Key findings showed that visceral fat – not subcutaneous fat or other fat metrics – was most strongly associated with higher levels of amyloid and tau proteins [2]. The researchers employed brain PET scans to measure these proteins, while MRI imaging quantified visceral and subcutaneous fat volumes.
Dr Mahsa Dolatshahi, lead author and postdoctoral researcher at MIR, emphasized the study’s midlife focus. She said: “This crucial result was discovered because we investigated Alzheimer’s disease pathology as early as midlife – in the 40s and 50s – when the disease pathology is at its earliest stages, and potential modifications like weight loss and reducing visceral fat are more effective as a means of preventing or delaying the onset of the disease [2].”
One of the study’s pivotal findings was that visceral fat accounted for 77% of the effect of high body mass index (BMI) on amyloid accumulation. Although prior research has linked obesity with cognitive decline, this study highlights the unique role of visceral fat in Alzheimer’s pathology. It also found that insulin resistance and low HDL (high-density lipoprotein, or “good cholesterol”) were associated with increased amyloid levels.
“A key implication of our work is that managing Alzheimer’s risk in obesity will need to involve targeting the related metabolic and lipid issues that often arise with higher body fat,” said senior study author Cyrus Raji, MD, PhD, associate professor of radiology at MIR [2].
Potential mechanisms
The researchers hypothesize that visceral fat may contribute to brain pathology through inflammation, insulin resistance and changes in lipid metabolism, all of which are associated with Alzheimer’s. These findings were reinforced by a related study from the same group, which demonstrated that higher visceral fat levels are associated with reduced cerebral blood flow – a critical factor in brain health [3]. Lower blood flow was particularly pronounced in Alzheimer’s-affected brain regions, such as the temporal lobe.
“This work will have a considerable impact on public health because nearly three out of four Americans are overweight or obese,” said Raji. “Knowing that visceral obesity negatively affects the brain opens up the possibility that treatment with lifestyle modifications or appropriate weight-loss drugs could improve cerebral blood flow and potentially lower the burden of and reduce the risk for Alzheimer’s disease [2].”
Prevention and public health
The findings emphasize the need for targeted interventions to reduce visceral fat during midlife. Lifestyle changes, such as diet and exercise, may be particularly effective when initiated before the onset of Alzheimer’s symptoms, and the study also raises the possibility of pharmacological approaches to manage obesity and its metabolic effects.
As Alzheimer’s cases continue to rise, identifying and addressing modifiable risk factors like visceral fat offers a proactive strategy to curb its impact. Early detection and prevention are vital to combating this disease, and this research demonstrates that addressing obesity is not just a physical health issue but could be critical for long-term cognitive health.
[1] https://www.alz.org/alzheimers-dementia/facts-figures
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC11272196/
