Alzheimer’s disease biomarker discovery in symptomatic and asymptomatic patients: Experimental approaches and future clinical applications

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Current treatments for AD are not as effective as needed, nor is there any definitive antemortem diagnostic. Understanding the biological processes that occur during AD onset and/or progression will improve disease diagnosis and treatment. Recent applications of microarray technologies for analysis of messenger (m) RNA expression profiles have elucidated distinct changes in the brain as a function of AD dementia initiation and progression. However, mRNA analysis underestimates posttranscriptional modifications and therefore provides only a partial view of the molecular changes in the AD brain. Combining mRNA studies with protein expression analysis may provide a more global picture of the biological processes associated with AD dementia. Information gathered could lead to the development of select biological indices (biomarkers) for guiding AD diagnosis and therapy. We will provide a brief background on AD, followed by a review on the applications of microarray, proteomics, as well as microRNA expression profile analysis to develop novel diagnostic strategies that may be useful for the diagnosis AD and for monitoring disease progression. The availability of biomarkers that promote early disease diagnosis, particularly among asymptomatic patients, will lead to the application of personalized medicine in AD.

Biomarkers and evolution in Alzheimer disease

“…Not only have miRNAs been shown to be aberrantly regulated in AD, but also this regulation has been implicated in AD pathogenesis (Wang et al, 2008). miRNAs have been tested in AD cerebrospinal fluid as a putative biomarker for the disease (Cogswell et al, 2008), and the search is on for other RNA-based potential diagnostic and therapeutic strategies (Ho et al, 2010). …”

Genome‐wide approaches in the study of microRNA biology

“…These works have brought to light the role of miRNAs as necessary for maintaining the robustness and stability of cellular systems when they are challenged with environmental stimuli. This critical connection to maintenance of homeostasis may help to explain the implication of miRNAs in disease systems ranging from immunological deficiencies,138 cancers and tumor metastasis,162 host–pathogen interactions,163 and even neurological diseases such as autism spectrum disorders164 and Alzheimer's disease 165. Effective diagnosis and therapies for these, and other diseases, may need to combine knowledge of both the protein and miRNA components of these pathways.…”

Environmental chemicals and microRNAs

“…There are approximately 900 known human miRNAs [8]. The aberrant expression of miRNAs has been linked to various human diseases, such as Alzheimer's disease, cardiac hypertrophy, altered heart repolarization, lymphomas, leukemias and cancer at several sites [9-25]. …”