Novel blood biomarkers that correlate with cognitive performance and hippocampal volumetry: Potential for early diagnosis of Alzheimer's disease

Hudd, Fred; Shiel, Anna; Harris, Matthew; Bowdler, Paul; McCann, Bryony; Tsivos, Demitra; Wearn, Alfie; Knight, Michael; Kauppinen, Risto; Coulthard, Elizabeth; White, Paul; Conway, Myra Elizabeth

Abstract

© 2019 - IOS Press and the authors. All rights reserved. Background: Differential diagnosis of people presenting with mild cognitive impairment (MCI) that will progress to Alzheimer's disease (AD) remains clinically challenging. Current criteria used to define AD include a series of neuropsychological assessments together with relevant imaging analysis such as magnetic resonance imaging (MRI). The clinical sensitivity and specificity of these assessments would be improved by the concomitant use of novel serum biomarkers. The branched chain aminotransferase proteins (BCAT) are potential candidates as they are significantly elevated in AD brain, correlate with Braak Stage, and may have a role in AD pathology. Objective: In this hypothesis-driven project, we aimed to establish if serum BCAT and its metabolites are significantly altered in AD participants and assess their role as markers of disease pathology. Methods: Serum amino acids were measured using a triple quadrupole mass spectrometer for tandem mass spectroscopy together with BCAT levels using western blot analysis, coupled with neuropsychological assessments and MRI. Results: We present data supporting a substantive mutually correlated system between BCAT and glutamate, neuropsychological tests, and MRI for the diagnosis of AD. These three domains, individually, and in combination, show good utility in discriminating between groups. Our model indicates that BCAT and glutamate accurately distinguish between control and AD participants and in combination with the neuropsychological assessment, MoCA, improved the overall sensitivity to 1.00 and specificity to 0.978. Conclusion: These findings indicate that BCAT and glutamate have potential to improve the clinical utility and predictive power of existing methods of AD assessment and hold promise as early indicators of disease pathology.

• Journal Article Type: Article
• Acceptance Date: Nov 24, 2018
• Online Publication Date: Feb 12, 2019
• Publication Date: Feb 1, 2019
• Deposit Date: Nov 27, 2018
• Publicly Available Date: Feb 21, 2019
• Journal: Journal of Alzheimer's Disease
• Print ISSN: 1387-2877
• Electronic ISSN: 1875-8908
• Publisher: IOS Press
• Peer Reviewed: Peer Reviewed
• Volume: 67
• Issue: 3
• Pages: 931-947
• DOI: https://doi.org/10.3233/JAD-180879
• Keywords: BCAT, glutamate, Alzheimers disease, biomarkers
• Public URL: https://uwe-repository.worktribe.com/output/852807
• Publisher URL: http://dx.doi.org/10.3233/JAD-180879
• Additional Information: Additional Information : The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180879
• Contract Date: Nov 28, 2018