Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Amyloid beta (A beta) is one of the proteins which aggregate in AD, and its key role in the disease pathogenesis is highlighted in the amyloid cascade hypothesis, which states that the deposition of A beta in the brain parenchyma is a crucial initiating step in the future development of AD. The sensitivity of instruments used to measure proteins in blood and cerebrospinal fluid has significantly improved, such that A beta can now successfully be measured in plasma. However, due to the peripheral production of A beta, there is significant overlap between diagnostic groups. The presence of pathological A beta within the AD brain has several effects on the cells and surrounding tissue. Therefore, there is a possibility that using markers of tissue responses to A beta may reveal more information about A beta pathology and pathogenesis than looking at plasma A beta alone. In this manuscript, using the amyloid cascade hypothesis as a starting point, we will delve into how the effect of A beta on the surrounding tissue can be monitored using biomarkers. In particular, we will consider whether glial fibrillary acidic protein, triggering receptor expressed on myeloid cells 2, phosphorylated tau, and neurofilament light chain could be used to phenotype and quantify the tissue response against A beta pathology in AD.
