title: Effects of baseline CSF α-synuclein on regional brain atrophy rates in healthy elders, mild cognitive impairment and Alzheimer's disease.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer's disease (AD). No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL), to patients with mild cognitive impairment (MCI) and AD.
  
  
  METHODS
  Baseline CSF α-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF α-synuclein on regional atrophy rates were tested in 1) four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem), and 2) all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF α-synuclein and diagnosis (testing NL versus MCI, and NL versus AD).
  
  
  RESULTS
  The effects of CSF α-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF α-synuclein, P=0.046) and brainstem (higher atrophy rates in subjects with lower CSF α-synuclein, P=0.063). CSF α-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037) and caudate (P=0.006).
  
  
  CONCLUSIONS
  With the possible exception of caudate and brainstem, the overall weak effects of CSF α-synuclein on atrophy rates in NL, MCI and AD argues against CSF α-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF α-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and reduce CSF α-synuclein levels, respectively.
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States of America ; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Insel
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States of America ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors.forename: Duygu
authors.initials: D
authors.lastname: Tosun
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Neurosciences, University of California, San Diego, California, United States of America.
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, California, United States of America ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D051844:alpha-Synuclein