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- Kurbatova, N., et al.
(författare)
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Urinary metabolic phenotyping for Alzheimer's disease
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Finding early disease markers using non-invasive and widely available methods is essential to develop a successful therapy for Alzheimer's Disease. Few studies to date have examined urine, the most readily available biofluid. Here we report the largest study to date using comprehensive metabolic phenotyping platforms (NMR spectroscopy and UHPLC-MS) to probe the urinary metabolome in-depth in people with Alzheimer's Disease and Mild Cognitive Impairment. Feature reduction was performed using metabolomic Quantitative Trait Loci, resulting in the list of metabolites associated with the genetic variants. This approach helps accuracy in identification of disease states and provides a route to a plausible mechanistic link to pathological processes. Using these mQTLs we built a Random Forests model, which not only correctly discriminates between people with Alzheimer's Disease and age-matched controls, but also between individuals with Mild Cognitive Impairment who were later diagnosed with Alzheimer's Disease and those who were not. Further annotation of top-ranking metabolic features nominated by the trained model revealed the involvement of cholesterol-derived metabolites and small-molecules that were linked to Alzheimer's pathology in previous studies.
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| 3. |
- Sunde, A. L., et al.
(författare)
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Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPlasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations. MethodsPlasma samples from 13 participants were stored at +4 degrees C and +18 degrees C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays. ResultsPhosphorylated tau 181 (p-tau181), phosphorylated tau 231 (p-tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4 degrees C and +18 degrees C. Amyloid-beta 40 (A beta 40) and amyloid-beta 42 (A beta 42) concentrations were stable for 24 h at +4 degrees C but declined when stored at +18 degrees C for longer than 6 h. This decline did not affect the A beta 42/A beta 40 ratio. DiscussionPlasma samples can be stored for 24 h at +4 degrees C or +18 degrees C and result in valid assay results for p-tau181, p-tau231, A beta 42/A beta 40 ratio, GFAP, and NfL. HIGHLIGHTSPlasma samples were stored for 24 h at +4 degrees C and +18 degrees C, mimicking clinical practice.Concentrations for Alzheimer's disease biomarkers were measured at six time-points.p-tau181, p-tau231, NfL, and GFAP concentrations were unchanged during the experiment.Storage at +18 degrees C affected A beta 40 and A beta 42 concentrations while storage at +4 degrees C did not. The A beta 42/A beta 40 ratio was unaffected.These plasma tests seem suitable for use in general practice.
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