TY - JOUR
T1 - Seeking environmental causes of neurodegenerative disease and envisioning primary prevention
AU - Spencer, Peter S.
AU - Palmer, Valerie S.
AU - Kisby, Glen E.
N1 - Funding Information:
We thank the communities affected by ALS-PDC for their assistance in helping us advance understanding of the causation of this disease . Research relating to Gulf War/Gulf Era veterans was funded by the U.S. Department of Veterans Affairs Cooperative Studies Program #500 contract to Durham VA, with subcontract to Oregon Health & Science University, Portland, Oregon.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of disease-affected individuals and communities, the results of which can provide an invaluable guide to steer cogent epidemiological and laboratory-based research.
AB - Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of disease-affected individuals and communities, the results of which can provide an invaluable guide to steer cogent epidemiological and laboratory-based research.
KW - Alzheimer disease
KW - Amyotrophic lateral sclerosis
KW - Atypical parkinsonism
KW - Colon cancer
KW - Cycad
KW - Dementia
KW - Guam, Kii Peninsula, West Papua
KW - Gulf War veteran
KW - Methylazoxymethanol
KW - Tauopathy
KW - Western Pacific ALS-PDC
KW - β-N-methylamino-L-alanine
UR - http://www.scopus.com/inward/record.url?scp=84963621639&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963621639&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2016.03.017
DO - 10.1016/j.neuro.2016.03.017
M3 - Article
C2 - 27050202
AN - SCOPUS:84963621639
VL - 56
SP - 269
EP - 283
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
ER -