Cerebrospinal Fluid Alzheimer’s Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort

Article type: Research Article

Authors: van Steenoven, Inger^{a; *} | Aarsland, Dag^{b; c} | Weintraub, Daniel^d | Londos, Elisabet^e | Blanc, Frédéric^f | van der Flier, Wiesje M.^g | Teunissen, Charlotte E.^h | Mollenhauer, Britⁱ | Fladby, Tormod^j | Kramberger, Milica G.^k | Bonanni, Laura^l | Lemstra, Afina W.^a | on behalf of the European DLB consortium

Affiliations: [a] Department of Neurology & Alzheimer Centre, VU University Medical Center, Amsterdam, The Netherlands | [b] Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institute, Stockholm, Sweden | [c] Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway | [d] Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA | [e] Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden | [f] Neuropsychology Unit and Geriatric Day Hospital (Strasbourg Resource and Research Memory Centre, CMRR) University Hospital of Strasbourg and ICube Laboratory, FMTS, University of Strasbourg and CNRS, Strasbourg, France | [g] Department of Neurology & Alzheimer Centre and Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [h] Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center Amsterdam, The Netherlands | [i] Paracelsus-Elena-Klinik, Kassel and University Medical Center, Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany | [j] Department of Neurology, Akershus University Hospital and Faculty of Medicine, University of Oslo, Norway | [k] Department of Neurology, University Medical Centre, Ljubljana, Slovenia | [l] Department of Neuroscience and Imaging and Clinical Science, and Aging Research Centre, G. d’Annunzio University, Chieti, Italy

Correspondence: [*] Correspondence to: Inger van Steenoven, MSc, VUmc Alzheimercentrum, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands. Tel.: +31 20 44 45 276; E-mail: [email protected].

Abstract: Background: Concomitant Alzheimer’s disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers. Objective: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB). Methods: We included 375 DLB patients, 164 Parkinson’s disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau. Results: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF. Conclusion: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.

Keywords: Amyloid beta-protein (1-42), biomarkers, cerebrospinal fluid, dementia with Lewy bodies, Lewy body disease, tau protein

DOI: 10.3233/JAD-160322

Journal: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 287-295, 2016