Changes in body fat due to obesity can contribute to Alzheimer’s disease: Study

Obesity-related changes in body fat can send harmful signals to the brain, disrupting immune system function, and potentially contribute towards worsening of Alzheimer’s disease, according to a new study.

The findings, published in the Molecular Neurodegeneration journal, offer fresh insight into the neurodegenerative condition and opens up an avenue for early intervention in people with metabolic risk for Alzheimer’s disease.

The ageing-related neurological disorder affects one’s cognition, memory and speech, and can eventually interfere with daily functions.

Researchers, led by those at the U.S.’ Houston Methodist Hospital, said the study moves beyond the traditional view of obesity as a general health risk.

Obesity is most commonly assessed by a value of 30 or higher body mass index. The metabolic condition can increase inflammation and vascular damage, potentially increasing risk of Alzheimer’s disease.

The team found that obesity increases levels of phosphatidylethanolamines (PEs) — a type of fat molecule — in body tissues, where it is packaged into tiny particles and carried to the brain.

In the brain, the PE particles disrupt communication between neurons, weaken immune system and promote buildup of amyloid proteins, which are naturally present but condense into clumps in Alzheimer’s disease — a hallmark of neurodegeneration.

“Obesity can change how signals travel to the brain. The good news is that this may be something we can treat. Instead of looking at Alzheimer’s risk tied to obesity as just a metabolic problem, this research suggests we may be able to target the process that connects those changes to the brain,” co-lead researcher Stephen Wong, distinguished chair in biomedical engineering, said.

The study employed an integrative ‘multi-omics’ approach combining lipidomics, single-nucleus RNA sequencing, proteomics, and high-resolution imaging to delineate the metabolic changes in tissues arising due to obesity.

Functional assessments were performed in mouse models of Alzheimer’s disease to evaluate the brain’s immune responses and behavioural outcomes.

“Our study reveals a critical role for PE (phosphatidylethanolamine) in coordinating immune-neuronal crosstalk under metabolic stress,” the authors wrote.

“These findings suggest that lipid remodeling serves as a structural nexus linking obesity to AD (Alzheimer’s disease) progression, and support the potential of lipid-directed interventions as therapeutic strategies for metabolic-risk-associated neurodegeneration,” they said.