Role of Amyloid β1–42 and Neuroimaging Biomarkers in Alzheimer‘s Disease

Abstract

Recent years have witnessed an enormous interest in the field of biomarkers of Alzheimer’s disease (AD). From an epidemiological standpoint, AD represents the most common dementing pathology in the elderly, and a fourfold increase in AD prevalence is anticipated to occur in the upcoming decades. Current estimates predict that over 80 million individuals will be affected by this neurodegenerative disorder by 2040 [1]. The pathophysiology of AD is complex and involves numerous distinct pathways, including amyloid-b (Ab) peptides aggregation with plaques formation (amyloid plaques) and hyperphosphorylation of the tau protein with deposition of neurofibrillary tangles. Such alterations ultimately lead to neuronal loss, synaptic integrity disruption and neuro degeneration [2]. The ‘amyloid cascade hypothesis’ remains the best accepted model for explaining AD [3]. Currently, the clinical diagnosis of AD is solely based on probabilistic criteria and postmortem examination remains to be the only means to make a final diagnosis [4,5]. In this context, the identification of bio markers in biological fluids that may allow an early presymptomatic diagnosis, as well as discrimination from other types of dementia, is eagerly awaited. In this article, we will focus our attention on Ab1–42 levels in the cerebrospinal fluid (CSF) as the core biochemical marker for the amyloidogenic process in AD. Extracellular senile plaques consist of Ab peptides, originating from the amyloid precursor protein via sequential proteolytic cleavages by b-secretase (b-site amyloid precursor protein-cleaving enzyme) and g-secretase [6]. Once released, Ab fragments may be present in solution and can be measured in the CSF and plasma [7]. The highly hydrophobic