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- Title
Salivary inflammatory biomarkers are predictive of mild cognitive impairment and Alzheimer's disease in a feasibility study.
- Authors
McNicholas, Kym; François, Maxime; Jian-Wei Liu; Doecke, James D.; Hecker, Jane; Faunt, Jeff; Maddison, John; Johns, Sally; Pukala, Tara L.; Rush, Robert A.; Leifert, Wayne R.
- Abstract
Alzheimer's disease (AD) is an insidious disease. Its distinctive pathology forms over a considerable length of time without symptoms. There is a need to detect this disease, before even subtle changes occur in cognition. Hallmark AD biomarkers, tau and amyloid-b, have shown promising results in CSF and blood. However, detecting early changes in these biomarkers and others will involve screening a wide group of healthy, asymptomatic individuals. Saliva is a feasible alternative. Sample collection is economical, non-invasive and saliva is an abundant source of proteins including tau and amyloid-β. This work sought to extend an earlier promising untargeted mass spectrometry study in saliva from individuals with mild cognitive impairment (MCI) or AD with age- and gender-matched cognitively normal from the South Australian Neurodegenerative Disease cohort. Five proteins, with key roles in inflammation, were chosen from this study and measured by ELISA from individuals with AD (n = 16), MCI (n = 15) and cognitively normal (n = 29). The concentrations of Cystatin-C, Interleukin-1 receptor antagonist, Stratifin, Matrix metalloproteinase 9 and Haptoglobin proteins had altered abundance in saliva from AD and MCI, consistent with the earlier study. Receiver operating characteristic analysis showed that combinations of these proteins demonstrated excellent diagnostic accuracy for distinguishing both MCI (area under curve = 0.97) and AD (area under curve = 0.97) from cognitively normal. These results provide evidence for saliva being a valuable source of biomarkers for early detection of cognitive impairment in individuals on the AD continuum and potentially other neurodegenerative diseases.
- Subjects
SOUTH Australia; PROTEIN analysis; ALZHEIMER'S disease diagnosis; SALIVA analysis; BIOMARKERS; PILOT projects; CYTOKINES; STATISTICS; STATISTICAL power analysis; BLOOD proteins; INFLAMMATION; MILD cognitive impairment; INTERLEUKIN-1; ALLELES; REGRESSION analysis; MATRIX metalloproteinases; COMPARATIVE studies; RANDOMIZED controlled trials; RESEARCH funding; MASS spectrometry; APOLIPOPROTEINS; ENZYME-linked immunosorbent assay; DESCRIPTIVE statistics; SENSITIVITY &; specificity (Statistics); GLOBULINS; RECEIVER operating characteristic curves; POLYMERASE chain reaction; DATA analysis; DATA analysis software; STATISTICAL sampling; LONGITUDINAL method; EVALUATION
- Publication
Frontiers in Aging Neuroscience, 2022, Vol 14, p01
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2022.1019296