How Excess Body Fat Impairs the Brain's Immune Defense in Alzheimer's Disease

Recent research from Purdue University challenges the long-held belief that fat has no role in neurodegenerative diseases. The studies reveal that excess fat within brain cells, particularly microglia and astrocytes, impairs the brain's natural immune functions, contributing to the progression of Alzheimer's disease.

The groundbreaking findings, published in the journal Immunity, indicate that excess lipid accumulation in these supportive brain cells hampers their ability to clear harmful proteins like amyloid beta and tau, which are hallmarks of Alzheimer's pathology. Specifically, the buildup of lipid droplets—fat storage structures—within microglia correlates with reduced capacity to phagocytose and remove amyloid plaques.

Chopra's team uncovered that in the presence of disease-related inflammation, microglia convert free fatty acids into triacylglycerol, which leads to overload and dysfunction. The enzyme DGAT2 plays a pivotal role in this process. Rather than overproducing DGAT2, the enzyme accumulates due to decreased degradation, causing microglia to divert fatty acids into fat stores, impairing their immune capacity.

These insights suggest that the accumulation of specific lipid molecules—the 'lipid plaques'—may be a key factor driving neuroinflammation and neurodegeneration. Interventions targeting this lipid pathway, such as inhibiting DGAT2 or promoting its breakdown, have shown promise in restoring microglial function, reducing lipid buildup, and improving neuronal health in animal models.

The research emphasizes that tackling fatty acid metabolism within the brain's immune cells could offer new therapeutic avenues for Alzheimer's disease. By focusing on lipid regulation, scientists aim to restore the brain’s natural defenses, ultimately slowing or reversing the effects of neurodegeneration.

This research not only redefines the role of lipids in brain health but also paves the way for innovative treatments that could disrupt disease progression at the cellular and molecular levels.

Source: https://medicalxpress.com/news/2025-09-fat-disables-brain-immune-shield.html