The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives
By R. Swerdlow, J. Burns, Shaharyar M. Khan. Biochimica et Biophysica Acta, 2013
714 citations recorded by the source corpus.
Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it.
Subfields: Molecular Biology, Physiology, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/d0760173f94759d3a732c354d3c64a8ed8c3b296
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Citations in the corpus
- Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease (2017, background): “The mitochondrial cascade hypothesis states that in sporadic, late-onset AD, loss of mitochondrial function associated with age affects the expression and processing of A PP initiating A accumulation [33].”
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “The mitochondrial cascade hypothesis proposes that mitochondrial dysfunction is the primary trigger for events leading to sporadic late AD onset [517].”