Neurodegenerative Processes In Alzheimer‘s Disease: An Overview of Pathogenesis With Strategic Biomarker Potential

Since Alzheimer's disease (AD) is the leading cause of senile dementia in the USA, affecting 15% of people over the age of 65 years and almost 50% of those aged over 85 years, the need for an adequate and early diagnosis as well as preventative measure against disease onset and progression is increasing. Epidemiological and molecular studies suggest that AD has multiple etiologies, including genetic mutations, genetic variations affecting susceptibility and environmental factors. All these aspects can promote the formation and the accumulation of insoluble amyloid-β and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker for the disease is crucial. While amyloid and amyloid-related compounds may be useful biomarkers in the early diagnosis of AD, the multitude of other characteristic features of AD presented in this article may be similarly appropriate. For example, genetic mutations play a role in a subset of AD patients (often with early disease onset and more severe disease progression), and genetic analysis could thus play a role in disease diagnosis. Similarly, oxidative damage to various proteins, nucleic acids and other cellular compounds, probably arising from mitochondrial abnormalities, is found early in the disease and may provide certain biochemical signatures of disease. Ultimately, specific assays for genetic, protein and oxidative profiles and mitochondrial abnormalities, as well as those for amyloid-β and its immunological response, may serve as a relevant group of biomarkers that could be informative to individuals regarding risk of disease, as well as for indicators of the progression of disease. Correspondingly, new developments in treatment options will probably be available.