Biomarkers for Alzheimer's Disease Early Diagnosis

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

Keywords: Alzheimer’s disease; biofluids; biomarkers; early diagnosis.

Figure 1

Schematic overview of invasive biomarkers. Different biomarkers have been used to detect early anatomical changes in the brains of people with mild cognitive impairment, including the atrophy of specific brain areas like the locus coeruleus or the hippocampus, and the presence of typical protein aggregates such as extracellular amyloid plaques or intracellular Tau-containing neurofibrillary tangles (upper panel). Additionally, biomarkers of Alzheimer’s disease (AD)-related degenerative processes like synaptic dysfunction, neuroinflammation, oxidative stress, or neuronal loss can be measured in the cerebrospinal fluid of AD patients. The detection of miRNAs represents a novel and promising tool for the early AD diagnosis (lower panel).

Figure 2

Schematic overview of noninvasive biomarkers: eyes, saliva, urine and blood. Besides fluid biomarkers (tears) that can be collected from the eyes, the promising advances in in vivo retinal imaging could provide an AD diagnosis tool in the near future. Blood-isolated brain secreted extracellular vesicles (BEVs) derive from three possible brain cell types: neural precursors, neurons and astrocytes. The content of this blood-isolated BEVs, mainly miRNAs, have been investigated as potential AD biomarker.