Clearance of beta-amyloid 42 (Aβ-42) and tau proteins in Alzheimers Disease (AD)

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Despite intense efforts to develop drugs for preventing and treating AD, no effective therapies are available yet, posing a growing burden at the personal, medical, and socioeconomic levels. AD is characterized by the production and aggregation of amyloid 0 (A0) peptides derived from amyloid precursor protein (APP), the presence of hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic inflammation leading to neuronal loss. A0 accumulation and hyperphosphorylated Tau are responsible for the main histopathological features of AD, A0 plaques, and neurofibrillary tangles (NFTs), respectively. However, the full spectrum of molecular factors that contribute to AD pathogenesis is not known. Non-coding (nc)RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) regulate gene expression at the transcriptional and posttranscriptional levels in various diseases, serving as biomarkers and potential therapeutic targets. There is rising recognition that ncRNAs have been implicated in both the onset and pathogenesis of AD. Here, the ncRNAs implicated post-transcriptionally in the main AD pathways and discuss the growing interest in targeting regulatory ncRNAs therapeutically to combat AD by using a series of multifunctional molecules that contained APP, and Tau-recognition moieties and E3 ligase-binding moieties to enhance APP, and Tau degradation. The goals involve the exploration into non-invasive biomarker screening for cognitive dementia related to Alzheimer’s Disease (AD) and in canine blood samples. The specific aims are towards the identification and development of non-invasive AD-related biomarkers for detection screening before the onset of pathophysiological symptoms related to cognitive deterioration seen in AD. The purpose of the project is concentration on the clearance of A0 and Tau through the liver.