Introduction
The neurotoxin β-N -methylamino-L -alanine (BMAA) (Supplementary Fig. 1) was hypothesized as an environmental factor responsible to the endemic amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) in Guam and other globally sporadic neurodegenerative diseases including ALS and Alzheimer’s disease (AD)1-4. Symbiotic cyanobacteria in the coralloid roots of cycad trees were demonstrated as the producer of BMAA in Guam5, which was followed by several studies showing positive detection of BMAA in diverse free-living cyanobacteria in seawater or freshwater environments6-14. Later some eukaryotic organisms such as dinoflagellates15,16 and diatoms17-19 were reported to produce this neurotoxin.
Significant bioaccumulation and biomagnification of BMAA were reported in zooplankton and various vertebrates (fish) and invertebrates (mussels, oysters) in Baltic Sea dominated by massive surface cyanobacterial blooms20, following the report on BMAA biomagnification in the Guam ecosystem5. Varied concentrations of BMAA (nd to ~7000 µg g-1) were detected in diverse resident animals suffering from cyanobacterial blooms in the South Florida aquatic ecosystem6. Six freshwater aquaculture products in different trophic levels also contained BMAA in the Taihu Lake Basin with chronic pollution of cyanobacterial blooms21. The feeding patterns (plankton-benthivorous) and increased age of fish leading to a higher concentration of BMAA was also found in the Lake Finjasjön in southern Sweden22. Muscle, liver, and brain tissue samples of a huge carp from the Lake Mascoma, as well as filtered aerosol samples contained BMAA23. Additionally, positive detection of BMAA was reported in mussels and other mollusks in French coasts24-26, in Sweden27,28, as well as in diverse filter-feeding mollusks or benthic gastropod in China29,30. Expectedly higher concentrations of BMAA [144~1836 µg g-1 wet weight (WW)] were detected in fin samples of sharks from South Florida31. These findings of BMAA in aquatic animals at different trophic levels demonstrate an exposure risk to BMAA through a diet of aquatic products.
The detection of BMAA in the brain tissues of both ALS-PDC patients from Guam4 and sporadic AD or ALS patients from the United States32 further support the linkage between BMAA and neurodegenerative diseases. Additionally, BMAA was shown to be mis-incorporated into proteins to replace L-serine33and following incorporation could slowly release this toxin as an endogenous source34. Vervets (Chlorocebus sabaeus ) fed a low-dose of BMAA over an extended period of time in fruit developed neurofibrillary tangles (NFT) and sparse β-amyloid deposits in the brain in contrast to control animals that were free from these protein deposits, which indicated that chronic exposure to the environmental BMAA can trigger neurodegeneration in vulnerable individuals35. Mathematical models of BMAA insertion into proteins suggest that the replacement of BMAA for L-serine in the SOD1 or β-amyloid protein could play a role in neurodegeneration36.
Although the presence of BMAA in cyanobacterial samples is consistent across many studies, the quantitation of BMAA in cyanobacterial samples vary widely and reflects different methods on different samples37-42. Interestingly, no BMAA was detected from cyanobacteria isolated from Chinese freshwater environments using LC-HILIC-MS/MS method38, but BMAA was detected in diverse mollusks and gastropod from marine ecosystem in China using the same method29,30. A recent review article described marine bivalves as having higher concentrations of BMAA, far more than most fish muscles, but with an exception for shark cartilage, which hinted that the source of BMAA in aquatic ecosystem requires further investigations43. In addition, the hypothesis of a causal relationship between BMAA and neurodegenerative disease relationship has also been criticized but without primary data and using selective sources only44. It is clear that additional studies would benefit this field. In the marine ecosystem in China, the absence of BMAA detection in cyanobacterial samples but ubiquity in diverse marine animals30,38 suggests that this may be a good study case to further examine biomagnification of BMAA.
The Jiaozhou Bay located in the Yellow Sea of China was selected as the survey area in the present study. Phytoplankton, zooplankton, mollusks, and crustacea samples were collected during four different seasons and analyzed for BMAA and its isomers β-aminomethyl-L -alanine (BAMA), 2,4-diaminobutyric acid (DAB) and N -(2-aminoethyl) glycine (AEG) in marine organisms of different trophic levels using an LC-MS/MS method. An additional 56 strains (belong to 5 genera) of diatoms isolated from Chinese seawater were cultured and scanned for these compounds. Bioaccumulation and magnification of BMAA in different marine organisms at different trophic levels in the Jiaozhou Bay were discussed in the present study.