Molecular Basis of Alzheimer’s Disease: Focus on Mitochondria

Issue title: Healthy Aging and Dementia Research

Guest editors: P. Hemachandra Reddy

Article type: Review Article

Authors: Oliver, Darryll M.A.^a | Reddy, P. Hemachandra^{a; b; c; d; e; f; g; h; *}

Affiliations: [a] Internal Medicine Department, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [b] Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [c] Garrison Institute on Aging, South West Campus, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [d] Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [e] Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [f] Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [g] Department of Speech, Language and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, United States | [h] Department of Public Health, Graduate School of Biomedical Sciences, Lubbock, TX, United States

Correspondence: [*] Correspondence to: P. Hemachandra Reddy, Ph.D., Professor of Internal Medicine, Cell Biology and Biochemistry, Neuroscience & Pharmacology and Neurology Departments, Texas Tech University Health Sciences Center, 3601 Fourth Street / 4B 207, Lubbock, TX 79430, United States, Email: [email protected].

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease, characterized by memory loss and multiple cognitive impairments. With the increased aging population, AD is a major health concern in society. Morphological and pathological studies revealed that AD is associated with the loss of synapses, defective mitochondria, and the proliferation of reactive astrocytes and microglia, in addition to the presence amyloid-β and phosphorylated tau in learning and memory regions of the brain in AD patients. AD occurs in two forms: early-onset familial and late-onset sporadic. Genetic mutations in APP, PS1, and PS2 loci cause familial AD. Multiple factors are reported to be involved in late-onset AD, including APOE4 genotype, polymorphisms in several gene loci and type 2 diabetes, traumatic brain injury, stroke, and age-related factors, including increased reactive oxygen species production and dysfunction in mitochondria. It is widely accepted that synaptic damage and mitochondrial dysfunction are early events in disease process. The purpose of this article is to highlight molecular triggers to the disease process. This article also reviews factors, including age, gender, lifestyle, epigenetic factors, and type 2 diabetes, that are involved in late-onset AD. This article also discusses recent developments in research of mitochondrial structure, function, physiology, dynamics, biogenesis, mitophagy, and mitochondrial DNA changes in healthy and diseased states.

Keywords: Alzheimer’s disease, familial Alzheimer’s disease, mitochondria, mitochondrial biogenesis, mitophagy, reactive oxygen species

DOI: 10.3233/JAD-190048

Journal: Journal of Alzheimer's Disease, vol. 72, no. s1, pp. S95-S116, 2019