New perspectives in the search for reliable biomarkers in Alzheimer disease

Abstract

-Background and Objectives:The search for accurate biomarkers in Alzheimer Disease (AD), on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient therapeutic strategies.A wide variety of potential biomarkers are has been identified by neuroimaging techniques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF) or blood. Recently, a growing number of studies are focused on the discovery of reliable bloodbased biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases.In this review, the latest challenges in the search for accurate biomarkers of AD is revised, in particular, an update in blood-based biomarkers is described in depth.Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72. Challenges in the discovery of potential biomarkers in Alzheimer DiseaseTo date there are no effective therapies to preserve normal brain function in potential future Alzheimer's disease (AD) patients. The absence of reliable biomarkers to identify cognitive normal individuals that will become early-stage AD patients support this fact. Therefore, this overlap between demented and non-demented population has limited the diagnostic accuracy of the current known biomarkers for AD. Due to the fact that neurological processes that finally result in dementia are assumed to be actively long before the first symptoms appear, the availability of diagnostic biomarkers could make a preclinical diagnostic testing and an early treatment of AD possible.A great variety of biomarkers of AD has been described using different approaches (Table 1). As Figure 1 shows, different strategies can be studied along AD progression for a better understanding of the disease and to enable an accurate identification of potential AD biomarkers. Currently, the most studied methods to identify markers of mild cognitive impairment (MCI) and AD are neuroimaging and molecular techniques based on cerebrospinal fluid (CSF). A systematic search on PubMed and Scopus databases was performed to find the most relevant studies and review papers. The key words used for this purpose were: "Alzheimer's disease", "Mild Cognitive Impairment", "biomarkers", "blood", "neuroimaging" and "neurodegenerative diseases" in various combinations. The articles selected were published in English from 2004 to 2015.Neuroimaging is a non-invasive technique which monitors brain regions and allows the subsequent identification and quantification of diagnostic and candidate biomarkers of dementia progression 1 . Magnetic resonance imaging (MRI) is the most widely used neuroimaging technique to investigate brain changes and neurodegeneration. Several longitudinal studies using MRI have been conducted with positive results 2,3 . After followup assessments, th...

A Bayesian hierarchical change point model with parameter constraints

“…neuroimaging) available, the majority are not available for routine use due to expense, risks, and the need for specialized equipment or laboratories. 20,21 Hence, it is critical to develop statistical methods that can be easily implemented to improve the prognosis of cognitive decline and to help triage patients when deciding whether further diagnostic biomarker testing is necessary.…”