CSF Tau, Aβ₄₂, and MHPG Differentiate Dementia with Lewy Bodies from Alzheimer's Disease

Article type: Research Article

Authors: Aerts, Marjolein B.^{a; b} | Esselink, Rianne A.J.^{a; b} | Claassen, Jugen A.H.R.^{b; c} | Abdo, Wilson Farid^d | Bloem, Bastiaan R.^{a; b} | Verbeek, Marcel M.^{a; b; e; *}

Affiliations: [a] Radboud University Nijmegen Medical Centre, Department of Neurology and Parkinson Center Nijmegen, Nijmegen, The Netherlands | [b] Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands | [c] Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine and Alzheimer Centre Nijmegen, Nijmegen, The Netherlands | [d] Radboud University Nijmegen Medical Centre, Department of Intensive Care Medicine, Nijmegen, The Netherlands | [e] Radboud University Nijmegen Medical Centre, Department of Laboratory Medicine, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: M.M. Verbeek, PhD, Radboud University Nijmegen Medical Centre, Department of Neurology, 830 LGEM, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +00 31 24 3615192; Fax: +00 31 24 3668754; E-mail: [email protected].

Abstract: Differentiating dementia with Lewy bodies (DLB) from Alzheimer's Disease (AD) can be difficult because of the substantial overlap in clinical features. Since deficits in serotonergic and dopaminergic pathways seem more pronounced in DLB patients, we investigated whether cerebrospinal fluid (CSF) analysis of neurotransmitter metabolites, in addition to brain-specific proteins, may improve the differentiation between DLB and AD. We retrospectively compared CSF concentrations of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the brain-specific proteins total tau (t-tau), phosphorylated tau protein (p-tau), and amyloid-β42 (Aβ42) in 45 patients with AD (mean age 71.6 years; 34 (76%) men; 44 probable AD, 1 definite) and 23 patients with DLB (mean age 71.6 years; 18 (78%) men; 6 possible DLB, 16 probable, 1 definite). The concentrations of all neurotransmitter metabolites, as well as those for t-tau and p-tau protein, were significantly lower in DLB compared to AD, irrespective of the diagnostic certainty (i.e., possible or probable). The currently used combination of Aβ42, p-tau, and t-tau yielded a sensitivity of 92.9% and a specificity of 90%. The addition of MHPG resulted in an increased sensitivity of 97.6% and a specificity of 95% for the discrimination between DLB and AD. In conclusion, the combination of MHPG and the brain specific proteins t-tau, p-tau, and Aβ42 in CSF were associated with the clinical diagnosis of DLB and discriminated between AD and DLB with high diagnostic accuracy, suggesting this combination as a potential biomarker for DLB.

Keywords: Alzheimer's disease, amyloid-β, cerebrospinal fluid, dementia with Lewy bodies, diagnosis, MHPG, neurotransmitter metabolites, tau

DOI: 10.3233/JAD-2011-110482

Journal: Journal of Alzheimer's Disease, vol. 27, no. 2, pp. 377-384, 2011