| Abstrakt: |
Background: The health benefits of odd‐chain saturated fatty acids (ocSAFA) have recently been recognized. We previously showed decreased unesterified ocSAFA in cerebrospinal fluid (CSF) of AD compared to MCI and cognitively healthy (CH). However, changes in ocSAFA relative to even‐chain saturated fatty acids (ecSAFA) have not been determined in other biofluids. Therefore, we aim to determine if levels of ocSAFA and ecSAFA may reveal AD pathology in urine. Methods: We used neuropsychology and CSF measures of Ab42 and T‐tau to classify groups of elderly subjects as cognitively healthy (CH) with negative Ab42 (CH‐Ab‐), cognitively healthy with positive Ab42 (CH‐Ab+), MCI, and AD. We collected urine after an overnight fast and quantified unesterified fatty acids (UFA) and esterified fatty acids (EFA) using gas chromatography coupled with negative‐ion chemical ionization mass spectrometry. For data normalization, we measured ocSAFA species (C15:0, C17:0, C19:0) and ecSAFA species (14:0, C16:0, C18:0, C20:0, C22:0, C24:0) as a proportion of the sum of all UFA or EFA > C14:0 in urine. We calculated group differences using ordinary ANOVA with Tukey's multiple comparison tests. Results: Urine unesterified C15:0 levels were significantly higher in AD than in MCI and CT (p = 0.0016). Similarly, esterified levels of ocSAFA were higher in AD than in MCI and CT (p<0.0001). Although Aβ42 levels in CH‐Aβ+ and AD are not significantly different, unesterified C15:0, esterified C17:0, C19:0, and total esterified ocSAFA were significantly higher in AD urine than in CH‐Aβ+. Urinary unesterified ecSAFA levels did not change in AD compared with CH and MCI. In contrast, esterified ecSAFA decreased in AD compared to CH. While esterified C16:0 decreased, esterified C18:0 increased in AD urine compared to CH and MCI. These changes result in a significant decrease in the C18:0/C16:0 ratio in AD (Fig. 1). The ratio of esterified ocSAFA to ocSAFA was higher in AD than CH and MCI (p<0.0001) (Fig. 2). Conclusions: These studies suggest that urine saturated fatty acids can reveal AD‐associated pathology. Therefore, measurement of urine fatty acids can be used to monitor AD‐linked biochemical pathways or to monitor therapies targeting saturated fatty acid metabolism in AD. [ABSTRACT FROM AUTHOR] |
