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Detection of urinary short‐chain dicarboxylic acids by GC/MS as a measurement of oxidative stress and mitochondrial function in Alzheimer's Disease
Author(s) -
Castor Katherine J,
Shenoi Sonia,
Rowshan Kiana,
Applegate Sarah,
Fonteh Alfred N,
Harrington Michael G
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1132.7
Subject(s) - urine , chemistry , creatinine , oxidative stress , oxidative phosphorylation , medicine , alzheimer's disease , succinic acid , endocrinology , biochemistry , chromatography , disease
Objectives To detect short‐chain dicarboxylic acids (DCAs) in urine from an aging cohort and determine whether they can be used as a measure of oxidative stress and mitochondrial function in Alzheimer's disease (AD). Methods We have developed a method to extract short‐chain DCAs from acidified urine using ethyl acetate, followed by separation, detection and quantification using gas chromatography coupled to isotope dilution negative ion chemical ionization mass spectrometry. Urine was obtained from volunteer study participants aged ≥ 75 years who have been classified in the following categories: cognitively normal (n = 59), mild cognitive impairment (n = 40), dementia of the AD type (n = 26), and other dementias (n = 10). Total DCA concentrations were normalized to creatinine and total protein levels in the urine and subjected to statistical analysis and correlations to established cerebrospinal fluid (CSF) biomarkers of AD (β‐amyloid and Tau protein levels). Results We can detect C3‐C10 DCAs by our method with a linear range between ≤ 0.20 – 100 ng and have determined that even chain DCAs make up 65–75% of the total with the highest percentage coming from succinic acid (C4, 30–50%). A negative correlation was found between succinic acid and Tau protein levels (P < 0.001). Additionally, a negative correlation was found between total DCA concentration in cognitively normal volunteers and their ®‐amyloid CSF levels while total DCA levels did not differ between groups. Conclusions Metabolic pathways such as oxidation and energy production that are associated with DCA metabolism may be involved in amyloid and Tau formation in normal aging but not in AD. This sensitive and specific method can be used to detect DCAs in biological fluids in disease biomarker studies and to determine pathological correlates. Support or Funding Information Research supported by the L.K. Whittier and Helen Posthuma Foundations