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Lack of evidence for a role of BMAA (β-N-methylamino-L-alanine) in human neurodegenerative disease
Citation:
Chernoff, N. Lack of evidence for a role of BMAA (β-N-methylamino-L-alanine) in human neurodegenerative disease. neurodegenerative diseases Summit, Los Angeles, CA, July 18 - 20, 2019.
Impact/Purpose:
General overview Presentation for the Neurodegenerative Diseases Summit. No new data included.
Description:
The compound BMAA has been postulated to play a causative role in four neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and Alzheimer’s disease that occur globally. The BMAA hypothesis is based on four contentions: 1. BMAA caused ALS/PDC due to consumption of animals that contained large quantities of cycad seeds where cyanobacteria-produced BMAA had bioaccumulated; 2. All of these diseases are sufficiently similar to enable BMAA to cause them; 3. Environmental exposures to BMAA are sufficient to cause the diseases; and 4. BMAA acts by producing neurofibrillary tangles due to its incorporation into proteins in place of serine and this is proven by animal studies and the existence of BMAA in the brains of sufferers of both ALS and Alzheimer’s. There are now data that collectively contradict these contentions. Analysis of the identical Guam food using more definitive analytical methods have shown no BMAA present. There are major differences between these four diseases in terms of the types of aberrant proteins and/or affected regions of the brain, and no evidence that one agent could induce them in different individuals. Analytical studies have often not identified BMAA in the environment, and when found, were quantities approaching the amounts thought to have induced ALS/PDC. Several well-designed, definitive studies have failed to find BMAA incorporation into proteins. Animal studies have used unrealistically high dose levels, and in the case of rodents, inappropriate routes of administration. Studies using accurate analytical techniques have not have not identified BMAA in the brains of former ALS or Alzheimer’s patients. The BMAA hypothesis as a causal factor for neurodegenerative diseases has not been verified.