CSF α-Synuclein Does Not Discriminate Dementia with Lewy Bodies from Alzheimer's Disease

Article type: Research Article

Authors: Reesink, Fransje E.^{a; *} | Lemstra, Afina W.^a | van Dijk, Karin D.^{a; b} | Berendse, Henk W.^a | van de Berg, Wilma D.J.^b | Klein, Martin^c | Blankenstein, Marinus A.^d | Scheltens, Philip^a | Verbeek, Marcel M.^f | van der Flier, Wiesje M.^{a; e}

Affiliations: [a] Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands | [b] Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands | [c] Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands | [d] Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands | [e] Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [f] Radboud University Nijmegen Medical Center, Department of Neurology, Depatment of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Alzheimer Centre, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: F.E. Reesink, MD, Departments of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Tel.: +31 2044400685; Fax: +31 204440715; E-mail: f.reesink@vumc.nl.

Note: [] Handling Associate Editor: Kaj Blennow

Abstract: In this study, we assessed whether cerebrospinal fluid (CSF) levels of the biomarker α-synuclein have a diagnostic value in differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also analyzed associations between CSF biomarkers and cognitive performance in DLB and in AD. We included 35 DLB patients, 63 AD patients, 18 patients with Parkinson's disease (PD), and 34 patients with subjective complaints (SC). Neuropsychological performance was measured by means of the Mini-Mental Status Examination (MMSE), Visual Association Test (VAT), VAT object-naming, Trail Making Test, and category fluency. In CSF, levels of α-synuclein, amyloid-β 1-42 (Aβ1-42), total tau (tau), and tau phosphorylated at threonine 181 (ptau-181) were measured. CSF α-synuclein levels did not differentiate between diagnostic groups (p=0.16). Higher ptau-181 and higher tau levels differentiated AD from DLB patients (p< 0.05). In DLB patients, lower Aβ1-42 and higher total tau levels were found than in SC and PD patients (p< 0.05). In DLB patients, linear regression analyses of CSF biomarkers showed that lower α-synuclein was related to lower MMSE-scores (β (SE) = 6(2) and p< 0.05) and fluency (β (SE) = 4(2), p< 0.05). Ultimately, CSF α-synuclein was not a useful diagnostic biomarker to differentiate DLB and/or PD (α-synucleinopathies) from AD or SC. In DLB patients maybe lower CSF α-synuclein levels are related to worse cognitive performance.

Keywords: Alzheimer's disease, biomarkers, cerebrospinal fluid, dementia with Lewy bodies, diagnosis, α-synuclein

DOI: 10.3233/JAD-2010-100186

Journal: Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 87-95, 2010