title: Amyloid-β and α-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson's disease.
abstract: BACKGROUND
  Cognitive impairment in early Parkinson's disease (PD) is common and distinct from early Alzheimer's disease. Predictors and mechanisms are only partially known, but α-synuclein, amyloid-β and tau dysmetabolism may be involved. Our aim was to study associations between cerebrospinal fluid biomarkers (CSF) and cognition in non-dementia PD compared to normal controls (NC) and non-PD patients with mild cognitive impairment (MCI non-PD).
  
  
  METHODS
  Patients were classified as having normal, subjective or mild cognitive impairment after cognitive screening. CSF levels of total α-synuclein (t-α-syn), amyloid-β (Aβ) 38, 40 and 42, total tau (T-tau) and phosphorylated tau (P-tau) were measured in 34 NC, 31 early, non-dementia PD and 28 MCI non-PD patients. A well validated neuropsychological test battery was administered.
  
  
  RESULTS
  In the PD group, 13 had normal cognition, 4 had subjective and 14 mild cognitive impairment. PD patients had significantly lower CSF biomarker levels of t-α-syn, Aβ38, 40 and 42, T-tau and P-tau compared to NC. Compared to MCI non-PD, t-α-syn, Aβ38 and 40, T-tau and P-tau were also lower, while Aβ42 was significantly higher in the PD group. Aβ38 and 40 correlated strongly with t-α-syn levels in PD. Lower Aβ42 was associated with decreased verbal learning, delayed verbal recall and response inhibition in PD.
  
  
  CONCLUSIONS
  While Aβ38, 40 and t-α-syn levels are strongly correlated, only lower Aβ42 was associated with reduced cognitive functions in early PD, mainly connected to medial temporal lobe-based cognitive functions.
authors.affiliation: Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway. Electronic address: aneolo@medisin.uio.no.
authors.forename: Ane Løvli
authors.initials: AL
authors.lastname: Stav
authors.affiliation: Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and, Society, Karolinska Institutet, Novum, 141 86 Stockholm, Sweden; Center for Age-Related Diseases, Stavanger University Hospital, 4000 Stavanger, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.affiliation: Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway.
authors.forename: Krisztina Kunszt
authors.initials: KK
authors.lastname: Johansen
authors.affiliation: Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Department of Psychology, University of Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Hessen
authors.affiliation: Department of Geriatric Psychiatry, Akershus University Hospital, 1478 Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Auning
authors.affiliation: Department of Neurology, Akershus University Hospital, 1478 Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000502:physiology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000523:psychology; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000523:psychology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Cerebrospinal fluid biomarkers; Cognitive impairment; Parkinson's disease; Pre-dementia