Alzheimer's linked to fat metabolism malfunction, research notes

By Will Chu

- Last updated on GMT

Alzheimer's disease accounts for between 60% and 80% of total dementia cases worldwide and represents a major cause of global morbidity and mortality. ©iStock/
Alzheimer's disease accounts for between 60% and 80% of total dementia cases worldwide and represents a major cause of global morbidity and mortality. ©iStock/
The metabolism of omega-3 and omega-6 unsaturated fatty acids in the brain may be linked with the progression of Alzheimer's disease.

According to a latest study, certain types of fat exhibit specific trends in the brains of Alzheimer's disease (AD) patients.

Specifically, faults in how unsaturated fatty acids (UFA’s) metabolise may play a role in driving AD progression and that these results provide further evidence for the metabolic basis of AD development.

"While this was a small study, our results show a potentially crucial and unexpected role for fats in the onset of dementia,”​ said co-study author, Dr Cristina Legido Quigley from King's College London.

“Most surprisingly we found that a supposedly beneficial omega3, DHA, actually increased with the progression of the disease.

"It is now important for us to build on and replicate these findings in a larger study and see whether it corroborates our initial findings."

Dietary supplementation with the omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) have been shown to improve cognitive performance.

Previous human studies have also reported promising effects on cognition in individuals receiving either DHA, EPA, or a combination of the two​.

Current thinking suggests the build-up of tau and amyloid proteins in the brain is the cause of memory problems in dementia

However, how small molecule metabolism in the brain is linked with the development and progression of AD has not been extensively researched and was the reason for this latest study.

UK-US collaboration

old man-alzheimers-memory
t is currently estimated that there are over 46 million people suffering from the disease worldwide, with the number of patients estimated to rise to 131.5 million by 2050. ©iStock

Collaborative research between King's College London and the National Institute on Aging in the US took brain tissue from 43 subjects ranging in age from 57 to 95 years old.

They noted the differences in small molecules contained in these samples from three groups: 14 subjects with healthy brains, 15 that had high levels of tau and amyloid proteins but didn't show memory problems and 14 clinically diagnosed Alzheimer's patients.

They also looked at three different areas in the brain, one that usually shows little tau and amyloid, one that shows more tau and another that shows more amyloid.

The main molecules that showed the most difference were six types of fats, including omega-3 and 6, which changed in quantity in certain locations in the brain.

The team also found that unsaturated fatty acids were significantly lower in quantity in subjects with Alzheimer’s compared to healthy subjects.

“We identified significant differences in the abundance of six UFAs in three brain regions with gradations in these metabolites being related to both severity of neuropathology at death,”​ the study concluded.

FA levels in the brain

Earlier evidence has looked at UFA levels in the brain of AD patients. One study​reported increased levels of 20 fatty acids in the brain of late stage AD patients.

Four of these species, i.e., oleic, linoleic, linolenic, and arachidonic acid were also shown to be reduced in the present study, whereas levels of DHA were consistent.

Another study​ measured fatty acids in both plasma and brain tissue samples and reported lower levels of esterified DHA in the AD group.

Along with the relatively small sample size., other imitation of the study was the difficulty in assigning metabolite identities to metabolite features within the dataset.

“With the advent of large publicly available metabolite databases, it is hoped that larger numbers of metabolites will be identified in future studies using these methods,”​ the study concluded.

Source: PLOS Medicine

Published online ahead of print: doi.org/10.1371/journal.pmed.1002266

“Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study.”

Authors: Stuart G. Snowden , Amera A. Ebshiana , Abdul Hye, Yang An, Olga Pletnikova, Richard O’Brien, John Troncoso, Cristina Legido-Quigley , Madhav Thambisetty

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