Year: 2010
Type: review
Abstract: We first proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD) in 2004. Our core assumptions were a person's genes determine baseline mitochondrial function and durability, this durability determines how mitochondria change with advancing age, and critical changes in mitochondrial function initiate other pathologies characteristic of AD. Since then several lines of investigation report data consistent with or supportive of our hypothesis. In particular, AD endophenotype studies suggest a strong maternal genetic contribution, and links between mitochondrial function, tau phosphorylation, and amyloid-beta (Abeta) amyloidosis are increasingly recognized. As predicted, AD therapies designed to reduce Abeta thus far have had at best very limited clinical benefits; our hypothesis identifies alternative therapeutic targets. While placing mitochondria at the apex of an AD cascade certainly remains controversial, it is increasingly accepted by the AD research community that mitochondria play an important role in the late-onset forms of the disease. Even if the mitochondrial cascade hypothesis proves incorrect, considering its assumptions could potentially advance our understanding of sporadic, late-onset AD.
Source: Journal of Alzheimer s Disease
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: Longitudial Study of Cardiorespiratory Fitness in Alzheimer's Disease, Energy Metabolism and Brain Changes with Age and Alzheimer's Disease, Cytochrome Oxidase Polymorphisms in Aging, General Clinical Research Center, Cardiorespiratory Fitness in Alzheimer's Disease, Protein Transduction Mediated Delivery to Mitochondria for Neurodegenerative Dise
OpenAlex ID: W1685999671