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 post-transcriptional 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.

Scheme 1

Selective alteration of functional synaptic proteins, e.g., a-type synapsin in synapses that are morphologically present may be an underlying mechanism in MCI cognitive impairment.

Scheme 2

Schematic subdivision of AD as clinical and biochemical entity at various functional levels within an organism. The top bracket embraces those levels of disease for which traditional medicine has been successful in the last two centuries (tip of the iceberg), such that only observable pathology is addressed. The lower bracket embraces the extended region accessible by personalized medicine attempting to define the disease at cellular/biochemical levels.