Validation of MicroRNA Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid
| Autor: | Douglas Galasko, Julie A. Saugstad, Trevor J. McFarland, Theresa A. Lusardi, Christina A. Harrington, Jay Ian Phillips, Jodi Lapidus, Jack Wiedrick, Ursula S. Sandau, Joseph F. Quinn, Babett Lind |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Apolipoprotein E medicine.medical_specialty Validation study Genotype Apolipoprotein E4 tau Proteins Total tau Disease Real-Time Polymerase Chain Reaction Article 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Alzheimer Disease Internal medicine microRNA Humans Medicine Aged Amyloid beta-Peptides Mini–Mental State Examination medicine.diagnostic_test business.industry General Neuroscience Reproducibility of Results General Medicine Peptide Fragments MicroRNAs Psychiatry and Mental health Clinical Psychology 030104 developmental biology Case-Control Studies Female Geriatrics and Gerontology business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 67:875-891 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-180539 |
| Popis: | We previously discovered microRNAs (miRNAs) in cerebrospinal fluid (CSF) that differentiate Alzheimer’s disease (AD) patients from Controls. Here we examined the performance of 37 candidate AD miRNA biomarkers in a new and independent cohort of CSF from 47 AD patients and 71 Controls on custom TaqMan® arrays. We employed a consensus ranking approach to provide an overall priority score for each miRNA, then used multimarker models to assess the relative contributions of the top-ranking miRNAs to differentiate AD from Controls. We assessed classification performance of the top-ranking miRNAs when combined with apolipoprotein E4 (APOE4) genotype status or CSF amyloid-β(42) (Aβ(42)):total tau (T-tau) measures. We also assessed whether miRNAs that ranked higher as AD markers correlate with Mini-Mental State Examination (MMSE) scores. We show that of 37 miRNAs brought forth from the discovery study, 26 miRNAs remained viable as candidate biomarkers for AD in the validation study. We found that combinations of 6–7 miRNAs work better to identify AD than subsets of fewer miRNAs. Of 26 miRNAs that contribute most to the multimarker models, 14 have higher potential than the others to predict AD. Addition of these 14 miRNAs to APOE4 status or CSF Aβ(42):T-tau measures significantly improved classification performance for AD. We further show that individual miRNAs that ranked higher as AD markers correlate more strongly with changes in MMSE scores. Our studies validate that a set of CSF miRNAs serve as biomarkers for AD, and support their advancement toward development as biomarkers in the clinical setting. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|