Mapping cellular transcriptosomes in autopsied Alzheimer's disease subjects and relevant animal models

Abstract

Alzheimer's disease (AD) is a late-onset and progressive neurodegenerative disorder characterized clinically by memory loss, impairment of other cognitive functions, and changes in behavior and personality. The overall aim of this review is to summarize recent advances in studies of AD progression and the use of animal models in gene expression studies of AD progression. Genetic causes of AD are known only for early-onset AD patients. For a majority of late-onset AD patients, causal factors are still unknown. Currently, there are no early detectable biomarkers for late-onset AD, and there is a lack of understanding of AD pathophysiology, particularly at the early stages of disease progression, before pathology develops. Human histopathological and biochemical studies provide valuable information regarding the last stages of AD pathogenesis. However, to understand early cellular changes in AD progression before symptoms develop, animal models are still our only alternative. Several research groups have created genetically engineered animal models, particularly models of the mouse, rat, fly, and worm, which have allowed us to better, understand the initiating events of AD progression. Recently, state-of-the-art methods have helped elucidate gene expression changes in affected and unaffected tissues from postmortem AD brains and from animal models developed for AD studies. These methods allow the investigation of mRNA-based transcriptosomal profiles of brain specimens from AD humans and transgenic animals. The major finding from these studies is that AD progression and pathogenesis involve multiple cellular pathways, which suggests that AD is a complex and heterogeneous disease.