Abnormal levels of unsaturated fatty acids may contribute to Alzheimer’s disease processes, as researchers found that six of these fats were linked to both brain abnormalities and cognitive symptoms.
In people with amyloid-beta plaques but no cognitive problems, the abnormalities were less pronounced, suggesting that when levels of these fatty acids became too abnormal, cognitive symptoms appear. The data supports the theory that Alzheimer’s is largely a metabolic condition — an idea that is currently gaining ground.
The study, “Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study,” was published in the journal PLOS Medicine.
Plenty of studies have investigated the typical plaques, made up of amyloid-beta, and tangles containing the protein tau, in Alzheimer’s disease. Because many people have these plaques and tangles without showing cognitive symptoms of Alzheimer’s, researchers at King’s College London in England and colleagues at the National Institute on Aging in Maryland figured other factors may be involved in the onset of symptoms.
To better understand how metabolism impacts disease, the research team studied the brains of 14 deceased Alzheimer’s disease patients, 14 healthy people (controls), and 15 people with typical Alzheimer’s brain abnormalities but who had cognitive symptoms while still alive.
The team chose an approach called metabolomics, which can provide information about a large array of metabolites in a tissue, allowing researchers to screen for changes without preconceived notions of what to look for.
They analyzed three brain regions: one that is usually dominated by amyloid aggregates, another that mostly shows tau deposits, and finally, an area usually spared from any brain abnormalities in Alzheimer’s patients (the cerebellum).
They found that the levels of six unsaturated fatty acids were higher in regions with Alzheimer’s abnormalities. The fatty acids could also be linked to the presence of cognitive problems.
Interestingly, in the area where amyloid plaque dominates the brain abnormalities, the three fatty acids linoleic acid, linolenic acid, and arachidonic acid were lower in patients than controls. People with brain abnormalities but no symptoms had levels between controls and patients.
On the other hand, docosahexanoic acid was increased, with highest levels in patients, somewhat lower among those without symptoms, and lowest in healthy people.
This observation made the researchers believe that, when deviations in the fatty acids reach a certain threshold, a tipping point is reached at which patients start developing symptoms.
In the cerebellum, abnormalities were detected, but did not follow any specific pattern, as in the other brain regions.
The findings also support earlier studies showing that dietary supplementation with the omega-3 fatty acids DHA and EPA improve cognition in both animal models and humans.
The team underscored that the fatty acids identified in the study are used as raw material for a host of other factors with known biological actions, including inflammation. Therefore, it is not surprising that these metabolites can drive disease processes that contribute to Alzheimer’s disease.