Then came the slow emergence of data showing connections between Agent Orange and specific cancers in the exposed military personnel. Over time, the realization that Agent Orange exposures either caused or contributed to higher rates of diabetes mellitus, peripheral nerve diseases, and cardiovascular disease became evident, but the burden of proof was compromised by disbelief or dismissal by Federal Government agencies due to their overlap with expected aging-associated disorders. Within the past 2 or 3 years, further evidence suggests that Agent Orange exposures also heightened the risk for Alzheimer’s and other neurodegenerative diseases. The work by Dr. Suzanne M. de la Monte and colleagues, published in the Journal of Alzheimer’s Disease Reports provides the first experimental evidence that even short-term Agent Orange exposures can initiate a path toward Alzheimer’s neurodegeneration.
The authors exposed human brain neuronal cells to two of the main herbicidal toxins used in Agent Orange, namely 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The results were astonishing. Both 2,4-D and 2,4,5-T damaged the function of mitochondria and caused visible evidence of neuronal degeneration before cell death. In addition, Agent Orange toxins caused oxidative stress, increased expression amyloid beta precursor protein which after cleavage, leads to amyloid plaque and toxic fibril buildup, caused tau pathology including increased Tau phosphorylation, and altered cholinergic enzyme expression, which is needed for cognitive functions.
These effects of Agent Orange represent the hallmark neuronal abnormalities in Alzheimer’s Disease and align with epidemiologic data highlighted in two recent reviews.
Agent Orange is just one of the rainbow herbicides developed by the U.S. military but manufactured by Dow, Monsanto and other companies. Although the U.S. discontinued the registered use of 2,4,5-T due to compelling evidence for its harmful effects, 2,4-D still broadly impacts global populations due to its widespread, uncontrolled inclusion in herbicide and pesticide products such that 1 in 3 Americans has biomarker evidence of 2,4-D exposures. The contributions of environmental 2,4-D and previously 2,4,5-T exposures to the alarming rates of Alzheimer’s disease and diabetes are concerning.
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NOTES FOR EDITORS
Dr. Suzanne M. de la Monte, MD, MPH
Department of Medicine, Rhode Island Hospital
Providence, RI, 02908
Telephone: +1 401-444 7364
Fax: +1 401-444-2939
Full Open Access Study
"Agent Orange Causes Metabolic Dysfunction and Molecular Pathology Reminiscent of Alzheimer’s Disease" (ADR-230046), scheduled for Volume 7, issue 1, https://content.iospress.com/articles/journal-of-alzheimers-disease-reports/adr230046
(published in the Journal of Alzheimer’s Disease Reports, Volume 7, Issue 1 (April 2023) by IOS Press.
About the Journal of Alzheimer’s Disease Reports (JADR)
Journal of Alzheimer's Disease Reports is an Open Access international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, hypotheses, and case reports. It is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer's disease. JAD Reports has a Journal Impact Factor of 3.2 according to Journal Citation Reports (Clarivate, 2023). iospress.com/jad-reports
About IOS Press
IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in health and life sciences (including neurosciences, medical informatics, cancer research, and rehabilitation) and computer sciences (including artificial intelligence, data science, and semantic web). In addition, we offer specialized services that support scientific advancement. iospress.com