Detection of BMAA in the human central nervous system.
Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid β-N-methylamino-l-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases [corrected]. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts.
Department of Ecology, Environment and Plant Sciences, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: lotta.berntzon@su.se.
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L
Berntzon
Department of Clinical Neuroscience, Karolinska Institute, SE-17176 Stockholm, Sweden. Electronic address: lars-olof.ronnevi@karolinska.se.
L O
LO
Ronnevi
Department of Ecology, Environment and Plant Sciences, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: birgitta.bergman@su.se.
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B
Bergman
Department of Ecology, Environment and Plant Sciences, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: johan.eriksson@su.se.
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J
Eriksson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000599:Amino Acids, Diamino / Q000097:blood* / Q000134:cerebrospinal fluid*; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid; D000087522:Cyanobacteria Toxins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009792:Oceans and Seas; D013548:Sweden; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; C001824:beta-N-methylamino-L-alanine
ALS; BMAA; CSF; blood; neurodegeneration; neurotoxin