The concentration of six unsaturated fatty acids in key brain regions are associated with Alzheimer disease (AD) cognitive symptoms and neuropathology, according to a study publishing in PLOS Medicine. Cristina Legido-Quigley of King's College London, UK, Madhav Thambisetty of National Institute on Aging, USA, and colleagues performed a nontargeted metabolic profiling study comparing the concentration of 100 structurally distinct fatty acid metabolites in brain tissue samples from older individuals enrolled in the Baltimore Longitudinal Study of Aging. The participants all had cognitive assessments in the year before death and detailed neuropathological assessments on autopsy. The participants fell into three groups: 14 people with healthy brains, 15 with the neuropathological proteins tau or amyloid in their brains but who didn't show memory problems, and 14 with AD. The metabolite levels were measured in samples from brain regions vulnerable to AD pathology (middle frontal and inferior temporal gyri) as well as those from a region resistant to AD pathology (cerebellum).
The researchers found that the levels of six unsaturated fatty acids (UFAs) (linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, oleic acid, and arachidonic acid) in the vulnerable brain regions were associated with AD.
As this study is observational, it is not clear whether dysregulation of UFA drives AD pathology or is a response to it. The authors also note that this is a small study due to limited availability of tissue samples with longitudinal cognitive assessments and detailed neuropathological assessments at death, and that in nontargeted metabolomics approaches like this one, not all metabolite features can be assigned identities. Thus, larger studies are needed to confirm the findings and may identify other metabolites associated with AD. Still, the authors conclude that this "work suggests that dysregulation of UFA's metabolism plays a role in driving AD pathology and that these results provide further evidence for the metabolic basis of AD pathogenesis."
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This research article appears in the PLOS Medicine Special Issue on Dementia, publishing each week throughout March.
Research Article
Funding:
The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu/) under European Medical Information Framework grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Association companies' in kind contribution for SGS and CLQ. This work has been supported by a grant to AAE from the Libyan Cultural attaché of Libyan embassy. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging for MT and YA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests:
The authors have declared that no competing interests exist.
Citation:
Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O'Brien R, et al. (2017) Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS Med 14(3): e1002266. doi:10.1371/journal.pmed.1002266
Author Affiliations:
Institute of Pharmaceutical Science, King's College London, London, United Kingdom
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
Laboratory of Behavioural Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America
Division of Neuropathology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
Department of Neurology, Duke University Medical School, Duke University, Durham, North Carolina, United States of America
Clinical and Translational Neuroscience Unit, Laboratory of Behavioural Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America
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Contact:
Cristina Legido-Quigley
King's College London
Institute of Pharmaceutical Science
Stamford Street
London, SE1 9NH
UNITED KINGDOM
cristina.legido_quigley@kcl.ac.uk
Madhav Thambisetty
National Institute on Aging
Baltimore, MD
UNITED STATES
thambisettym@mail.nih.gov
Journal
PLoS Medicine