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

Issue title: Mini-Forum: Roles of Amyloid-β and Tau Phosphorylation in Neuronal Repair and Protection

Guest editors: Garth Bissette

Article type: Research Article

Authors: Koudinov, Alexei^{a; b; c; d; *} | Kezlya, Elena^e | Koudinova, Natalia^{a; b; c} | Berezov, Temirbolat^{a; b; c; d}

Affiliations: [a] Berezov Research Laboratory, Russian Academy of Medical Sciences, Moscow, Russia | [b] Orechovich Institute of Biomedical Chemistry, RAMS, Moscow, Russia | [c] Neurobiology of Lipids, http://www.neurobiologyoflipids.org, Moscow, Russia, Rehovot, Israel | [d] Department of Biochemistry, Department of Biochemistry, School of Medicine, Peoples' Friendship University of Russia, Moscow, Russian Federation | [e] Interhospital Medical Center “Intermedcenter”, Moscow, Russia | Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA

Correspondence: [*] Corresponding author: Alexei Koudinov, P.O. Box 1665, Rehovot 76100 Israel. E-mail: [email protected].

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.

Keywords: Alzheimer's disease, amyloid-β, amyloid-β protein precursor, apolipoprotein E, cholesterol, Down's syndrome, high density lipoprotein, hippocampus, inclusion-body myositis, lipid peroxidation, lipoproteins, low density lipoprotein, markers, neuromuscular junctions, Niemann Pick's disease, phospholipids, synaptic plasticity, tau

DOI: 10.3233/JAD-2009-1202

Journal: Journal of Alzheimer's Disease, vol. 18, no. 2, pp. 381-400, 2009