Cerebrospinal Tau, Phospho-Tau, and Beta-Amyloid and Neuropsychological Functions in Parkinson’s Disease Yaroslau Compta, MD, 1 Marı ´a J. Martı ´, MD, PhD, 1 * Naroa Ibarretxe-Bilbao, PhD, 2 Carme Junque ´, PhD, 2 Francesc Valldeoriola, MD, PhD, 1 Esteban Mun ˜oz, MD, PhD, 1 Mario Ezquerra, PhD, 1 Jose Rı ´os, BSc, 3 and Eduardo Tolosa, MD, FRCP 1 1 Movement Disorders Unit, Neurology Service, Institut Clı´nic de Neurocie`ncies (ICN), Institut d’Investigacions Biome`diques August Pi i Sunyer (IDIBAPS), Centro de Investigacio´n en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clı´nic, Barcelona, Catalonia, Spain 2 Department of Psychiatry and Clinical Psychobiology IDIBAPS, CIBERNED, Faculty of Medicine, University of Barcelona, Catalonia, Spain 3 Statistics and Methodologic Support Unit, Unitat d’Avaluacio´, Suport i Prevencio´(UASP), Hospital Clı´nic, IDIBAPS, Barcelona, Catalonia, Spain Abstract: Alzheimer’s disease (AD)-pathology may play a role in Parkinson’s disease (PD)-related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho-tau, and beta-amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho-tau, and beta- amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological test- ing of fronto-subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phos- pho-tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta-amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho-tau were associated with impaired memory and naming. In PDND, CSF beta-amyloid was related with phonetic fluency. These findings suggest underlying AD-pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta-amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dys- function. Ó 2009 Movement Disorder Society Key words: Parkinson’s disease; dementia; cerebrospinal fluid; tau; beta-amyloid; neuropsychological function Dementia is common in Parkinson’s disease (PD), and a substantial proportion of patients develop this complication as the disease progresses. 1–3 The impact of PD-dementia (PDD) in disease evolution 4,5 and the eventual introduction of effective disease modifying strategies justify the search of PDD risk markers. Both the spread of Lewy-type pathology to neocortical regions 6,7 and Alzheimer’s disease (AD)-type lesions in terms of hyperphosphorylated tau (phospho-tau) and beta-amyloid aggregates 6,8,9 have been implicated in PDD. The latter pathological association and the find- ing of increased tau and phospho-tau and decreased beta-amyloid levels in cerebrospinal fluid (CSF) from AD patients 10 suggest that these CSF proteins also might constitute dementia markers in PD. To date, few studies have partially assessed CSF levels of these pro- teins in PDD, 11–13 with two of them showing lower CSF beta-amyloid compared with both controls and nondemented PD patients 12 or to controls. 13 Cognitive deficits detected using validated neuropsy- chological tests are also possible markers of risk for Potential conflict of interest: None reported. Additional Supporting Information may be found in the online version of this article. *Correspondence to: Dr. Marı ´a J. Martı ´, Movement Disorders Unit, Neurology Service, Hospital Clı ´nic de Barcelona, c./Villarroel 170, 08036 Barcelona, Spain. E-mail: mjmarti@clinic.ub.es Received 12 January 2009; Revised 11 March 2009; Accepted 17 March 2009 Published online 30 September 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mds.22594 2203 Movement Disorders Vol. 24, No. 15, 2009, pp. 2203–2210 Ó 2009 Movement Disorder Society