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Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease

2009; Wiley; Volume: 120; Issue: 4 Linguagem: Inglês

10.1111/j.1600-0404.2008.01150.x

1600-0404

John Pablo, Sandra Anne Banack, Paul Alan Cox, Terence E. Johnson, Spyridon Papapetropoulos, Walter G. Bradley, Andreas K. Buck, Deborah C. Mash,

Neurological diseases and metabolism

Acta Neurologica ScandinavicaVolume 120, Issue 4 p. 216-225 Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease J. Pablo, J. Pablo Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorS. A. Banack, S. A. Banack Institute for Ethnomedicine, Jackson Hole, WY, USASearch for more papers by this authorP. A. Cox, P. A. Cox Institute for Ethnomedicine, Jackson Hole, WY, USASearch for more papers by this authorT. E. Johnson, T. E. Johnson Thermo Fisher Scientific, San Jose, CA, USASearch for more papers by this authorS. Papapetropoulos, S. Papapetropoulos Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorW. G. Bradley, W. G. Bradley Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorA. Buck, A. Buck Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorD. C. Mash, D. C. Mash Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this author J. Pablo, J. Pablo Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorS. A. Banack, S. A. Banack Institute for Ethnomedicine, Jackson Hole, WY, USASearch for more papers by this authorP. A. Cox, P. A. Cox Institute for Ethnomedicine, Jackson Hole, WY, USASearch for more papers by this authorT. E. Johnson, T. E. Johnson Thermo Fisher Scientific, San Jose, CA, USASearch for more papers by this authorS. Papapetropoulos, S. Papapetropoulos Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorW. G. Bradley, W. G. Bradley Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorA. Buck, A. Buck Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this authorD. C. Mash, D. C. Mash Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USASearch for more papers by this author First published: 15 September 2009 https://doi.org/10.1111/j.1600-0404.2008.01150.xCitations: 257 Deborah C. Mash, PhD, Department of Neurology D4-5, 1501 NW 9th Ave, Miami, 33136 FL, USATel.: +305 243 5888Fax: +305 243 3649e-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Objective – The aim of this study was to screen for and quantify the neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and non-neurological controls. BMAA is produced by cyanobacteria found in a variety of freshwater, marine, and terrestrial habitats. The possibility of geographically broad human exposure to BMAA had been suggested by the discovery of BMAA in brain tissues of Chamorro patients with ALS/Parkinsonism dementia complex from Guam and more recently in AD patients from North America. These observations warranted an independent study of possible BMAA exposures outside of the Guam ecosystem. Methods – Postmortem brain specimens were taken from neuropathologically confirmed cases of 13 ALS, 12 AD, 8 HD patients, and 12 age-matched non-neurological controls. BMAA was quantified using a validated fluorescent HPLC method previously used to detect BMAA in patients from Guam. Tandem mass spectrometric (MS) analysis was carried out to confirm the identification of BMAA in neurological specimens. Results – We detected and quantified BMAA in neuroproteins from postmortem brain tissue of patients from the United States who died with sporadic AD and ALS but not HD. Incidental detections observed in two out of the 24 regions were analyzed from the controls. The concentrations of BMAA were below what had been reported previously in Chamarro ALS/ Parkinsonism dementia complex patients, but demonstrated a twofold range across disease and regional brain area comparisons. The presence of BMAA in these patients was confirmed by triple quadrupole liquid chromatography/mass spectrometry/mass spectrometry. Conclusions – The occurrence of BMAA in North American ALS and AD patients suggests the possibility of a gene/environment interaction, with BMAA triggering neurodegeneration in vulnerable individuals. References 1 Cox PA, Banack SA, Murch SJ et al. Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid. 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HPLC method validation and separation of β-N-methylamino-l-alanine (BMAA) in acid-hydrolyzed postmortem human brain matrix. A) Full-range (24–35 min) chromatograms of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatized, acid-hydrolyzed non-neurological human brain tissue. Identifiable peaks of AQC-derivatized l-valine (26.8 min) and l-methionine (28.1 min) are evident with and without spiked BMAA. Dashed area is shown expanded below. B) Identification of BMAA (retention time = 29.7 min) across experimental condition. (A, purple) Synthetic BMAA standard alone (no brain tissue), (B, green) control human brain tissue spiked with BMAA prior to acid hydrolysis, and (C, pink) control hydrolyzed human brain tissue spiked with BMAA prior to derivatization. Note the absence of BMAA in (trace D, orange) control human brain tissue without added BMAA and E (blue) AQC blank (no tissue extract). The standard and co-elution amino acid peaks were obtained in 60 min according to the method of Murch et al. [Proc Natl Acad Sci USA 2004;101(33):12228–31]. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Filename Description ANE_1150_sm_Fig S1.tif41.2 MB Supporting info item Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume120, Issue4October 2009Pages 216-225 ReferencesRelatedInformation