title: Detection of cyanotoxins, β-N-methylamino-L-alanine and microcystins, from a lake surrounded by cases of amyotrophic lateral sclerosis.
abstract: A cluster of amyotrophic lateral sclerosis (ALS) has been previously described to border Lake Mascoma in Enfield, NH, with an incidence of ALS approximating 25 times expected. We hypothesize a possible association with cyanobacterial blooms that can produce β-N-methylamino-L-alanine (BMAA), a neurotoxic amino acid implicated as a possible cause of ALS/PDC in Guam. Muscle, liver, and brain tissue samples from a Lake Mascoma carp, as well as filtered aerosol samples, were analyzed for microcystins (MC), free and protein-bound BMAA, and the BMAA isomers 2,4-diaminobutyric acid (DAB) and N-(2-aminoethyl)glycine (AEG). In carp brain, BMAA and DAB concentrations were 0.043 μg/g ± 0.02 SD and 0.01 μg/g ± 0.002 SD respectively. In carp liver and muscle, the BMAA concentrations were 1.28 μg/g and 1.27 μg/g respectively, and DAB was not detected. BMAA was detected in the air filters, as were the isomers DAB and AEG. These results demonstrate that a putative cause for ALS, BMAA, exists in an environment that has a documented cluster of ALS. Although cause and effect have not been demonstrated, our observations and measurements strengthen the association.
authors: Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA. sandra@ethnomedicine.org.
authors: Sandra Anne
authors: SA
authors: Banack
authors: Cheyenne Regional Medical Group, Cheyenne, WY 82001, USA. tracie.a.caller@dartmouth.edu.
authors: Tracie
authors: T
authors: Caller
authors: Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. patricia.l.henegan@hitchcock.org.
authors: Patricia
authors: P
authors: Henegan
authors: Department of Biological Sciences, University of New Hampshire, Durham, NH 03824, USA. jim.haney@unh.edu.
authors: James
authors: J
authors: Haney
authors: Department of Biological Sciences, University of New Hampshire, Durham, NH 03824, USA. amurby@unh.edu.
authors: Amanda
authors: A
authors: Murby
authors: Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA. james@ethnomedicine.org.
authors: James S
authors: JS
authors: Metcalf
authors: Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA. jpowell@ethnomedicine.org.
authors: James
authors: J
authors: Powell
authors: Institute for Ethnomedicine, PO Box 3464, Jackson, WY 83001, USA. paul@ethnomedicine.org.
authors: Paul Alan
authors: PA
authors: Cox
authors: Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. elijah.w.stommel@hitchcock.org.
authors: Elijah
authors: E
authors: Stommel
mesh_terms: D000599:Amino Acids, Diamino / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000209:etiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002347:Carps / Q000254:growth & development; D002853:Chromatography, Liquid; D000458:Cyanobacteria / Q000254:growth & development* / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D004784:Environmental Monitoring; D005068:Eutrophication; D020387:Food Chain; D006801:Humans; D060106:Lakes / Q000737:chemistry* / Q000382:microbiology; D057230:Limit of Detection; D008099:Liver / Q000737:chemistry; D052998:Microcystins / Q000032:analysis* / Q000633:toxicity; D018482:Muscle, Skeletal / Q000737:chemistry; D009513:New Hampshire; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D052998:Microcystins; D014874:Water Pollutants, Chemical; C001824:beta-N-methylamino-L-alanine
references: Toxicon. 2011 Apr;57(5):730-8
references: 21329717
references: Fed Proc. 1964 Nov-Dec;23:1368-9
references: 14236153
references: Acta Neurol Scand. 2004 Oct;110(4):267-9
references: 15355492
references: Toxicon. 2013 Aug;70:179-83
references: 23660330
references: Harmful Algae. 2010 Sep 1;9(6):620-635
references: 21057660
references: PLoS One. 2014;9(1):e84578
references: 24392143
references: Chest. 2007 Jan;131(1):187-94
references: 17218574
references: Toxicon. 2014 Nov;90:167-73
references: 25123936
references: Neuroepidemiology. 2005;24(3):141-50
references: 15650320
references: Toxins (Basel). 2010 Dec;2(12):2837-50
references: 22069578
references: Environ Toxicol. 2005 Jun;20(3):293-300
references: 15892067
references: Arch Neurol. 1990 Jan;47(1):38-41
references: 2294892
references: PLoS One. 2012;7(11):e49043
references: 23145061
references: Mar Drugs. 2007 Oct 12;5(4):136-50
references: 18463733
references: PLoS One. 2013;8(12):e83406
references: 24349504
references: Neurology. 2003 Sep 23;61(6):750-6
references: 14504316
references: Toxicon. 2006 Oct;48(5):580-9
references: 16928388
references: J Microbiol Methods. 2006 Jun;65(3):542-50
references: 16290299
references: Sci Total Environ. 2014 Jan 15;468-469:457-63
references: 24055662
references: Amyotroph Lateral Scler. 2009;10 Suppl 2:41-3
references: 19929730
references: Neurology. 1969 Nov;19(11):1029-37
references: 5388071
references: Amyotroph Lateral Scler. 2009;10 Suppl 2:101-8
references: 19929741
references: Neurology. 2003 Sep 23;61(6):742-9
references: 14504315
references: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13380-3
references: 14612559
references: Science. 2014 Jul 25;345(6195):455-9
references: 25061210
references: Clin Infect Dis. 1999 Jun;28(6):1191-6; quiz 1197-8
references: 10451151
references: Calif Med. 1957 Jun;86(6):385-8
references: 13426814
references: Med Hypotheses. 2013 Feb;80(2):142-5
references: 23246360
references: Int J Health Geogr. 2014;13:1
references: 24383521
references: Neurology. 1992 Jul;42(7):1336-40
references: 1620343
references: Ann Neurol. 1980 Dec;8(6):612-9
references: 7212649
references: Neuroepidemiology. 2008;31(1):28-32
references: 18535397
references: J Ethnopharmacol. 2006 Jun 15;106(1):97-104
references: 16457975
references: Amyotroph Lateral Scler. 2009;10 Suppl 2:109-17
references: 19929742
references: Environ Microbiol. 2008 Mar;10(3):702-8
references: 18237305
references: Environ Health Perspect. 2009 Jul;117(7):1095-100
references: 19654919
references: Indian J Microbiol. 2010 Oct;50(4):468-73
references: 22282617
references: Neurology. 2003 Aug 12;61(3):387-9
references: 12913204
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5074-8
references: 15809446
references: Environ Int. 2013 Sep;59:303-27
references: 23892224
references: Mar Drugs. 2012 Feb;10(2):509-20
references: 22412816
references: Neurology. 1985 Feb;35(2):193-8
references: 3969206
references: N Engl J Med. 1980 Feb 14;302(7):365-70
references: 7351928
references: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12228-31
references: 15295100
references: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9252-7
references: 20439734
references: Amyotroph Lateral Scler Frontotemporal Degener. 2013 May;14 Suppl 1:33-43
references: 23678878
references: Am J Epidemiol. 2003 Jan 15;157(2):149-57
references: 12522022
references: Crit Rev Toxicol. 2008;38(2):97-125
references: 18259982
references: Lancet. 1986 Apr 26;1(8487):965
references: 2871252
references: Emerg Infect Dis. 2002 Jan;8(1):37-43
references: 11749746
references: Clin Infect Dis. 2008 Jan 1;46(1):61-9
references: 18171215
references: Am J Epidemiol. 1966 Jan;83(1):54-73
references: 5910221
references: Ann Neurol. 1981 Oct;10(4):341-50
references: 7316487
references: Neurology. 2002 Mar 26;58(6):956-9
references: 11914415
references: Eur J Cell Biol. 2009 Jun;88(6):315-24
references: 19324456
references: Toxicon. 2011 Aug;58(2):187-94
references: 21704054
references: J Nerv Ment Dis. 1953 Feb;117(2):135-9
references: 13061952
references: Neurology. 1954 Jun;4(6):438-48
references: 13165883
references: Fed Proc. 1964 Nov-Dec;23:1343-5
references: 14236144
references: Lancet. 1998 Jan 10;351(9096):114
references: 9439505
references: Acta Neurol Scand. 2009 Oct;120(4):216-25
references: 19254284
references: Toxicon. 2010 Nov;56(6):868-79
references: 20561540