What initiates Alzheimer’s disease histology changes in those with late-onset Alzheimer's disease (LOAD) is unclear. An association between advancing age, Alzheimer's disease, histology changes, and Alzheimer's disease incidence suggests brain aging-related factors may play a role or even initiate the disease. Brain energy metabolism and mitochondrial function change with advancing age and in Alzheimer's disease, leading some to propose a “mitochondrial cascade hypothesis” in which bioenergetic changes are hypothesized to initiate Alzheimer's disease histology and clinical decline. In this Meet-the-Expert, Russell Swerdlow discusses how this idea has evolved over past decades, its current contributions to the Alzheimer's disease field, and how it might impact future Alzheimer's disease research.
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