Amyloid-β,Tau Protein,and Oxidative Changes as a Physiological Compensatory Mechanism to Maintain CNS Plasticity under Alzheimer's Disease and Other Neurodegenerative Conditions

Abstract

In this review, we propose that the neurodegenerative changes in the neurochemistry of amyloid-β (Aβ) aggregation, tau phosphorylation, cytoskeleton rearrangement, oxidative stress, and lipid peroxidation in Alzheimer's disease (AD), and a number of other neurodegenerative diseases, are secondary pathological features. In fact, we believe that these phenomena represent natural compensatory mechanisms for impaired primary neurodegeneration, membrane dynamic deterioration, and/or associated failures of neurotransmission, synaptic function, and neuroplasticity. Physiologically, Aβ, lipid peroxidation, and tau protein may function to sense changes in activity-dependent membrane properties and therefore biochemically modulate membrane lipid homeostasis for more efficient synaptic action. As such, the previously proposed therapeutic tackling of amyloid, tau, oxidative stress, and other brain disease markers may have no ability to cure AD or other devastating central nervous system pathologies and peripheral nervous system diseases. This unfortunate realization provides a wake-up call to the neuroscience community, demanding open-minded approach.