Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer’s Disease

Niklas Mattsson; Philip Insel; Duygu Tosun; Jing Zhang; Clifford R Jack Jr; Douglas Galasko; Michael Weiner; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1371/journal.pone.0085443

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Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer’s Disease

Journal article

Open access

Peer reviewed

Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer’s Disease

Niklas Mattsson, Philip Insel, Duygu Tosun, Jing Zhang, Clifford R Jack Jr, Douglas Galasko, Michael Weiner and Alzheimer’s Disease Neuroimaging Initiative

PloS one, Vol.8(12), e85443

2013

DOI: 10.1371/journal.pone.0085443

PMCID: PMC3877372

PMID: 24392009

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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). Discussion: 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.

Humans

Middle Aged

Organ Size

Male

Cognitive Dysfunction - cerebrospinal fluid

Cognitive Dysfunction - pathology

Alzheimer Disease - cerebrospinal fluid

Case-Control Studies

Alzheimer Disease - pathology

Alzheimer Disease - diagnosis

Atrophy

alpha-Synuclein - cerebrospinal fluid

Aged, 80 and over

Brain - pathology

Female

Aged

Cognitive Dysfunction - diagnosis

Details

Title: Subtitle: Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer’s Disease
Creators: Niklas Mattsson - 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
Philip Insel - Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, California, United States of America
Duygu Tosun - 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
Jing Zhang - Department of Pathology, University of Washington, Seattle, WA, United States of America
Clifford R Jack Jr - Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States of America
Douglas Galasko - Department of Neurosciences, University of California, San Diego, California, United States of America
Michael Weiner - 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
Alzheimer’s Disease Neuroimaging Initiative (Institution)
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: PloS one, Vol.8(12), e85443
DOI: 10.1371/journal.pone.0085443
PMID: 24392009
PMCID: PMC3877372
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: U01 HL096917 / NHLBI NIH HHS P50 AG005131 / NIA NIH HHS R01-AG041851 / NIA NIH HHS R01 AG011378 / NIA NIH HHS U01 AG024904 / NIA NIH HHS P50 AG008702 / NIA NIH HHS ES019277 / NIEHS NIH HHS U01-AG0324904 / NIA NIH HHS U01 NS082137 / NINDS NIH HHS NS082137 / NINDS NIH HHS R01 AG041851 / NIA NIH HHS R01 AG037551 / NIA NIH HHS P30 AG010129 / NIA NIH HHS R01-AG011378 / NIA NIH HHS U01-HL096917 / NHLBI NIH HHS ES016873 / NIEHS NIH HHS ES007033-6364 / NIEHS NIH HHS U01 AG032438 / NIA NIH HHS R01 AG033398 / NIA NIH HHS U01 AG1048 / NIA NIH HHS NS057567 / NINDS NIH HHS AG033398 / NIA NIH HHS R01 NS057567 / NINDS NIH HHS U24 AG021886 / NIA NIH HHS NS062684-6221 / NINDS NIH HHS P30 AG013846 / NIA NIH HHS K01 AG030514 / NIA NIH HHS R01 ES019277 / NIEHS NIH HHS P01 AGO5131 / PHS HHS R01-AG037551 / NIA NIH HHS P01AG020206 / NIA NIH HHS ES004696-5897 / NIEHS NIH HHS P01 AG020206 / NIA NIH HHS R01 ES016873 / NIEHS NIH HHS P30 ES007033 / NIEHS NIH HHS
Language: English
Date published: 2013
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051594702771

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