Dietary Exposure to an Environmental Toxin Triggers Neurofibrillary Tangles and Amyloid Deposits in the Brain
Overview
Affiliations
Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.
Serine metabolism in aging and age-related diseases.
Shan S, Hoffman J Geroscience. 2024; 47(1):611-630.
PMID: 39585647 PMC: 11872823. DOI: 10.1007/s11357-024-01444-1.
The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.
Bedlack R, Li X, Evangelista B, Panzetta M, Kwan J, Gittings L Ann Neurol. 2024; .
PMID: 39503319 PMC: 11683184. DOI: 10.1002/ana.27126.
Chatziefthimiou A, Metcalf J, Glover W, Powell J, Banack S, Cox P Toxicon X. 2024; 23:100199.
PMID: 38974839 PMC: 11225906. DOI: 10.1016/j.toxcx.2024.100199.
Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.
Varma C, Luo E, Bostrom G, Bathini P, Berdnik D, Wyss-Coray T Alzheimers Dement. 2024; 20(8):5460-5480.
PMID: 38946666 PMC: 11350037. DOI: 10.1002/alz.14038.
Bishop S, Solonenka J, Giebelhaus R, Bakker D, Li I, Murch S Toxins (Basel). 2024; 16(4).
PMID: 38668594 PMC: 11053616. DOI: 10.3390/toxins16040169.