AUTHOR=Dan Liang , Zhang Zhaohui TITLE=Alzheimer’s disease: an axonal injury disease? JOURNAL=Frontiers in Aging Neuroscience VOLUME=15 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1264448 DOI=10.3389/fnagi.2023.1264448 ISSN=1663-4365 ABSTRACT=

Alzheimer’s disease (AD) is the primary cause of dementia and is anticipated to impose a substantial economic burden in the future. Over a significant period, the widely accepted amyloid cascade hypothesis has guided research efforts, and the recent FDA approval of an anti- amyloid-beta (Aβ) protofibrils antibody, believed to decelerate AD progression, has further solidified its significance. However, the excessive emphasis placed on the amyloid cascade hypothesis has overshadowed the physiological nature of Aβ and tau proteins within axons. Axons, specialized neuronal structures, sustain damage during the early stages of AD, exerting a pivotal influence on disease progression. In this review, we present a comprehensive summary of the relationship between axonal damage and AD pathology, amalgamating the physiological roles of Aβ and tau proteins, along with the impact of AD risk genes such as APOE and TREM2. Furthermore, we underscore the exceptional significance of axonal damage in the context of AD.