Circulating Biomarker Panels in Alzheimer's Disease

Abstract

The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

Functional Significance and Predictive Value of MicroRNAs in Pediatric Obesity: Tiny Molecules with Huge Impact?

“…The sequence of most miRNAs is conserved across species, and some miRNAs are expressed in a tissue-specific manner. As such, it is not surprising that they are increasingly studied as biomarkers in the context of many diseases, for example cancer [33], Alzheimer's disease [34], and cardiovascular diseases [35], just to name a few of them, and recently also in the context of obesity. …”

Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

“…However, these measurements involve invasive lumbar puncture for routine assessment of disease [26]. Neuroimaging techniques, such as positron emission tomography and magnetic resonance imaging, provide more conclusive evidence of AD pathogenesis [27]. These procedures are used to identify neurodegenerative disease markers, but to do so, they need to be executed late in disease progression –too late to initiate successful preventive or effective therapeutic measures [28].…”

Circulating microRNA-144-5p is associated with depressive disorders

“…MicroRNAs are some of the most studied and well characterized among small noncoding RNAs. [13][14][15][16][17].…”