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P2‐251: SERUM ACYLCARNITINE LIPIDS AS BIOMARKERS OF PRECLINICAL ALZHEIMER'S DISEASE
Author(s) -
Huguenard Claire,
Cseresznye Adam,
Evans James,
Crawford Fiona,
Mullan Michael,
Abdullah Laila
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2658
Subject(s) - chemistry , medicine , mitochondrion , endocrinology , orbitrap , mass spectrometry , beta oxidation , oxidative phosphorylation , fatty acid , oxidative stress , biochemistry , chromatography
Background: There is now substantial evidence for a role of mitochondria dysfunction in Alzheimer’s disease (AD) which is characterized by decreased mitochondria function and increased oxidative stress. Mitochondrial dysfunction in AD is accompanied by decreased bioenergetics reflected by reduced brain glucose utilization and the capacity to perform beta-oxidation in the brain regions that are affected early in the disease process. We hypothesized that free carnitine and acylcarnitines reflecting changes in mitochondrial lipid transport/beta-oxidation occur prior to the onset of AD. Methods: We examined serum aclycarnitines from a longitudinal cohort of cognitively healthy subjects (n 1⁄4 198), a subset of whom converted to mild cognitive impairment (MCI) or AD within 2 to 3 years. Serum acylcarnitine extracts containing labelled acylcarnitines mixture were subjected to Hydrophilic Interaction Liquid Chromatography (HILIC) and mass spectrometry using a Q Exactive Hybrid QuadrupoleOrbitrap Mass spectrometer (Thermo Scientific) in a positive ion mode acquired with FTMS using scheduled parallel reaction monitoring at 17,500 resolution. Results: We observed significant differences in the levels of mediumand very long-chain fatty acid (VLCFA)-containing acylcarnitine species in serum from control subjects relative to those who converted to MCI/AD. Several medium-chain fatty acid (MCFA)-containing acylcarnitine species were elevated in MCI/AD converters compared to controls who stayed cognitively intact. Interestingly, VLCFA containing species were decreased in MCI/AD converters compared to subjects who remained cognitively intact over 2 to 3 years. A combined panel of these acylcarnitine species had a greater than 80% accuracy for providing a correct classification of preclinical MCI/ AD. Conclusions: These findings suggest that mitochondria related acylcarnitine abnormalities can be detected in serum of subjects with preclinical MCI/AD and could serve as biomarkers of early AD. Future studies are required to validate these findings in independent cohorts with a larger sample size to validate the use of serum acylcarnitines as predictors of preclinical AD.