HQ Team
September 25, 2025: Excess fat present in the brain’s immune cells impairs their ability to combat diseases such as Alzheimer’s, research from US-based Purdue University reveals.
The excess fat was found in the glial cells of the brain, such as microglia, which are responsible for immune defence and waste removal, and astrocytes that are crucial for the blood-brain barrier and structural support.
Oligodendrocytes, which play a crucial role in myelination in the central nervous system, are a third common glial cell.
“This insight opens a path to lipid biology-based neuroimmune therapies that could treat diseases like Alzheimer’s by enhancing microglial function and neuronal health,” according to a Purdue statement.
Most of the current Alzheimer’s drug development targets the primary pathologies of the disease — plaques of a misfolded protein called amyloid beta and tangles of the protein tau. Purdue researchers focused on the abnormally fat-rich cells surrounding diseased regions of the brain.
Fatty acid
In earlier works, the researchers showed that, in the presence of disease, astrocytes release a fatty acid that is toxic to brain cells and linked mitochondrial dysfunction in neurons with fat deposits in glial cells during ageing — a major risk factor for neurodegeneration.
In the current findings, the researchers found that excess fat in the microglia impairs the brain’s immune cells in fighting diseases.
“In our view, directly targeting plaques or tangles will not solve the problem; we need to restore the function of immune cells in the brain,” Gaurav Chopra, the lead researcher, said.
“We’re finding that reducing the accumulation of fat in the diseased brain is the key, as accumulated fat makes it harder for the immune system to do its job and maintain balance.
“By targeting these pathways, we can restore the ability of immune cells like microglia to fight disease and keep the brain in balance, which is what they’re meant to do,” he said.
Lipid droplets
More than 100 years ago, Alois Alzheimer identified abnormalities in the brain of a woman with the disease that now bears his name, including plaques, tangles and cells filled with droplets of fatty compounds called lipids.
Until recently, these lipid droplets were dismissed as by-products of disease. The links the researchers have found between neurodegenerative disease and fats in microglia and astrocytes strongly suggest otherwise.
“It is not the lipid droplets that are pathogenic, but the accumulation of these droplets is bad,” Chopra said.
“We think the composition of lipid molecules that accumulate within brain cells is one of the major drivers of neuroinflammation, leading to different pathologies, such as ageing, Alzheimer’s disease and other conditions related to inflammatory insults in the brain.
“The specific composition of these lipid plaques may define particular brain diseases,” Chopra said.
Microglia and triacylglycerol
The researchers also examined microglia, which clear out debris, such as misfolded proteins like amyloid beta and tau, by absorbing and breaking them down through a process called phagocytosis.
Images of brain tissue from people with Alzheimer’s disease showed amyloid beta plaques surrounded by microglia.
Microglia located within 10 micrometers of these plaques contained twice as many lipid droplets as those farther away. These lipid droplet-laden microglia, closest to the plaques, cleared 40% less amyloid beta than ordinary microglia from brains without disease.
Microglia, when in contact with plaques and disease-related inflammation, produced an excess of free fatty acids.
While microglia normally use free fatty acids as an energy source, the researchers discovered that the microglia closest to amyloid beta plaques convert these free fatty acids to triacylglycerol, a stored form of fat, in such large quantities that they become overloaded and immobilised by their own accumulation.
The formation of these lipid droplets depends on age and disease progression, becoming more prominent as Alzheimer’s disease advances.
“While most recent work in this area has focused on the genetic basis of the disease, our research paves the way for understanding how lipids and their pathways within the brain’s immune cells can be targeted to restore their function and combat the disease,” said Priya Prakash, a first co-author of the study.
