The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

Abstract

AbstractAlzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.