Affiliations: [a] Faculty of Health and Life Sciences, University of the West of England, Bristol, UK
| [b] Dementia Research Group, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK
| [c] Clinical Research and Imaging Centre (CRICBristol), University of Bristol, Bristol, UK
Correspondence:
[*]
Correspondence to: Myra E. Conway, Faculty of Health and Life Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK. Tel.: +44 117 328 3552; Fax: +44 117 328 2904; E-mail: myra.conway@uwe.ac.uk.
Note: [1] These authors contributed equally to this work.
Abstract: 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.
