Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain

Cox, Paul Alan; Da, Davis; Mash, Deborah C.; Metcalf, James S.; Banack, Sandra Anne

doi:10.1098/rspb.2015.2397

Cited by 196 publications

(146 citation statements)

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“…One of the most debated hypotheses has been the dietary intake of a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine. There are basic laboratory and animal evidences that this compound promotes both NFT and β-amyloid deposits [45,46], similar to the deposit found in the brain of Chamorros affected individuals.…”

Section: Als Foci In the Worldmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis Descriptive Epidemiology: The Origin of Geographic Difference

Logroscino

Piccininni

2019

Neuroepidemiology

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Amyotrophic lateral sclerosis (ALS) epidemiology has rapidly developed in the last 30 years alongside the evolving changes in concepts in the field of clinical ALS and also due to the recent proposals of new classification system for motor neuron diseases. Many of these changes in the clinical scenario have been determined through the results of ALS population-based studies conducted in the last 20 years primarily in Europe. All the evidences converge to show that ALS risk is different across continents and ethnicities. In a European registry consortium named EURALS, ALS incident cases were drawn from a source population comprising almost 24 million people across Europe (ALS cases: 1028) and the estimated incidence was 2.2 per 100,000 person-years (py) for the general population. In contrast, other population-based studies have measured the lowest incidence in East Asia to be 0.89 per 100,000 py and in South Asia to be 0.79 per 100,000 py. A large part of Africa, Latin America and Asia does not have any population-based studies. The origin of geographic difference in ALS incidence is a matter of debate. Probably, this is partly due to genes (C9ORF72) and partly due to environmental risk factors. The rapid disappearance of ALS Foci in Guam, Kii, and West Guinea underline the importance of changes in lifestyle and environmental factors. The Global Burden of Disease, a project aiming to describe the burden of all diseases and injuries across all the countries of the world with a standardized protocol, has collected heterogeneous sources of data to estimate the burden of motor neuron diseases. The demographic changes related to increased expectation of life and the growth of the world population indicate that the load of motor neuron disease is rapidly moving toward 400 thousand prevalent cases. The burden is expected to shift toward Asia and Africa in the next decades for the rapid increase of expectation of life of countries with high demographic impact.

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Section: Als Foci In the Worldmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis Descriptive Epidemiology: The Origin of Geographic Difference

Logroscino

Piccininni

2019

Neuroepidemiology

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“…BMAA is a neurotoxic amino acid which can be incorrectly insert into the polypeptide chains of brain proteins and then lead to protein misfolding, a hallmark characteristic of A plaque in AD patients (Mulligan and Chakrabartty, 2013). Recent research found that chronic dietary exposure to cyanobacterial toxin BMAA triggered NFT and A deposits in the brain and increased the risk of AD (Cox et al, 2016). Other cyanobacteria produced neurotoxins including saxitoxin and anatoxin- may further lead to neurological diseases, especially in the process of aging (Brenner, 2013).…”

Section: The Influence Of Gut Microbiota On Neurochemical and Metabolmentioning

confidence: 99%

Alzheimer’s disease and gut microbiota

Wang

Jin

2016

Sci. China Life Sci.

300

188

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“…The importance of biofilms and biofilm-dispersing agents in the prevention of Alzheimer's disease, particularly L-serine, is eloquently illustrated in the observations of Cox et al As an ethnobiologist, Dr. Cox was particularly fascinated with the markedly increased incidence of Lou Gehrig's, Parkinson's, and Alzheimer's diseases among the Chamorro people of Guam [84]. This was attributed to a unique diet high in beta-Methylamino-L-alanine (BMAA), a neurotoxic substance [84].…”

Section: Topical Systemicmentioning

confidence: 99%

“…This was attributed to a unique diet high in beta-Methylamino-L-alanine (BMAA), a neurotoxic substance [84]. Meanwhile, distant Ogimi villagers on the Japanese island of Okinawa who ate a diet of tofu and seaweed that contained large quantities of L-serine did not have these diseases, nor did they have high rates of arthritis [82].…”

Section: General Paresis Of the Insane And Alzheimer's Diseasementioning

confidence: 99%

Penicillin: The Old/New Wonder Drug

Allen¹,

Hossain²,

Abidi³

et al. 2017

Adv Tech Biol Med

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Penicillin (PCN) has been shown to treat psoriasis effectively and be curative in many cases. Streptococcus is the organism responsible for beginning the process and has previously escaped detection by moving intracellularly or by forming biofilms. The treatment is low dose for many months and thus is similar to rheumatic fever. Arthritis has been shown to be caused by biofilm-forming dental and Lyme spirochetes, and these organisms, like the streptococcus in psoriasis, have escaped detection. Penicillin, plus a biofilm-dispersing agent is effective in treating arthritis in which tissue destruction has not already occurred.Alzheimer's disease has been shown to be caused by those same spirochetes involved in arthritis, and, is in every way, similar to the dementia of neurosyphilis caused by Treponema pallidum. These organisms make biofilms that induce B amyloid and a Toll-like receptor 2 response leading to tissue destruction. Penicillin given prior to the organisms arrival in the brain (or before they create biofilms) would effectively prevent dementia in Alzheimer's as it does in syphilis. We have shown that biofilm-forming staphylococci are integral to the etiology of atopic dermatitis. Along with standard corticosteroid therapy, antibacterial treatment, as opposed to antibiotics, appears to be a better treatment in AD because all the organisms are multi-drug resistant and 60% are MRSA or MSRE. Treatment with PCN in psoriasis, arthritis, and syphilis, has thus far not led to resistance and may actually prevent resistance by killing organisms before they make biofilms and share resistance genes. rash [11]. The cutaneous manifestation typically accompanies the pharyngeal infection with the rash emerging due to erythrogenic toxins produced by the bacterium [10]. Treatment remains a ten-day course of oral penicillin VK or erythromycin, or a single intramuscular injection of penicillin G benzathine. If administered within 1 week of onset of acute pharyngitis, acute renal failure may be prevented [12]. Rheumatic feverLikewise, penicillin has equally revolutionized the treatment of rheumatic fever and the subsequent cardiac complications. Acute rheumatic fever occurs 2-3 weeks following infection of the pharynx by Group A streptococcus (GAS) [13]. Manifestations of acute rheumatic fever include arthritis, chorea, erythema marginatum and most importantly, carditis. Reinfection by GAS notably leads to valvular destruction and eventual heart failure [14]. While the reason exactly why infection by GAS causes rheumatic fever has yet to be determined, current hypotheses stipulate a relationship between the M protein of the bacterium, biofilm formation, and molecular mimicry between antibodies against bacterial proteins and cardiac membranes. Work by Catanzaro et al. noted that the development of rheumatic fever required living streptococci throughout the convalescent period, making penicillin treatment and prophylaxis essential [15].Treatment of acute rheumatic fever involves penicillin in alternate roles. Preventi...

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Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain

Cited by 196 publications

References 50 publications

Amyotrophic Lateral Sclerosis Descriptive Epidemiology: The Origin of Geographic Difference

Amyotrophic Lateral Sclerosis Descriptive Epidemiology: The Origin of Geographic Difference

Alzheimer’s disease and gut microbiota

Penicillin: The Old/New Wonder Drug

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