title: Cerebrospinal fluid α-synuclein and Lewy body-like symptoms in normal controls, mild cognitive impairment, and Alzheimer's disease.
abstract: BACKGROUND
  Reduced cerebrospinal fluid (CSF) α-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co-occurrence of Lewy body pathology is common in Alzheimer's disease (AD) patients, but it is unknown if reduced CSF α-synuclein is associated with Lewy body-like symptomatology in AD.
  
  
  OBJECTIVE
  Determine associations between CSF α-synuclein and Lewy body-like symptomatology.
  
  
  METHODS
  We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6-7.8). We tested associations between baseline CSF α-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration.
  
  
  RESULTS
  Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF α-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF α-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI).
  
  
  CONCLUSIONS
  The associations of low CSF α-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF α-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification.
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA Department of Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Mackin
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Insel
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA Department of Psychiatry, University of California, San Francisco, CA, USA Mental Health Service, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Mohlenhoff
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000523:psychology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005260:Female; D006212:Hallucinations / Q000134:cerebrospinal fluid* / Q000523:psychology; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000523:psychology; D008297:Male; D009483:Neuropsychological Tests; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Alpha-synuclein; Alzheimer's disease; cerebrospinal fluid; cognition; hallucinations; tau