{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:24:54Z","timestamp":1791998694871,"version":"4.4.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is a multifaceted neurodegenerative disorder with complex etiology, often associated with histological markers of oxidative stress, inflammation, and disturbances in calcium homeostasis. Traditionally, amyloid\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -peptides (A\u03b2) have been considered key contributors to these pathological processes. However, emerging evidence suggests a protective role for A\u03b2 and the enzymes involved in its production. This article further explores the hypothesis published by us a decade before that posits amyloid\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -peptides and the \u03b2-secretase enzyme (BACE1) are part of an intentionally designed cellular defense mechanism against metal toxicity. This challenges the conventional understanding of their roles in AD pathogenesis. It is not until this BACE1 system, primarily the associated amyloid plaque deposit sites, are saturated with heavy and other metals and the exposure to these cations continues to influx oxidative ions into the brain, do the indications of neurodegeneration begin to become symptomatic. Until this metal oversaturation takes place, the system \u2013 A\u03b2 and the enzymes involved in its production and conveyance \u2013 keeps the oxidative potential of the metal toxins sequestered extracellularly and out of the way of the neuron\u2019s intracellular activities.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2025.1550709","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T11:58:40Z","timestamp":1743163120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Reevaluating the role of amyloid \u03b2-peptides in Alzheimer\u2019s disease: from pathogenic agents to protective chelation 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