Since past research has demonstrated that abnormal levels of certain biomarkers can be found in CSF as well as in the blood of patients with AD, considerable investigations have been on-going to determine the diagnostic utility of these biomarkers. The following is a list of the key CSF and blood biomarkers that may have the potential to help in the assessment of AD. Assays for most of these biomarkers are commercially available:
Amyloid beta (AB) are peptides released by the proteolytic cleavage of the amyloid precursor protein (APP) and can be detected in both CSF and blood. APP is an integral membrane protein that may play a role in neuroregeneration and regulation of neural activity.
It is believed that the role of the AB peptides in normal humans is mainly of a protective function. Evidence suggests that AB serves a beneficial role in humans as it may have antimicrobial activity, tumor suppression properties, sealing or plugging leaks in the blood brain barrier, promoting the recovery from brain injury, and regulating synaptic function.
The release of the various AB peptides causes the buildup of fragments that cluster together and form larger deposits called amyloid plaques. These plaques appear to have a toxic effect on neurons and to disrupt cell-to-cell communication. Research has shown that the intracellular deposition of amyloid plaques in the brain may be an early driving force in the pathophysiology of AD.
The AB42 peptide: Considerable studies have focused on the AB peptide, AB42, which is the key AB peptide deposited in amyloid plaques. Because the AB42 peptide is deposited in the amyloid plaques instead of remaining in solution, low levels of AB-42 in the CSF have been found associated with AD. Therefore, low levels of AB42 in CSF may be a key biomarker to assess the pathology of AD.
AB42/AB40 Ratio: In addition to measuring the CSF levels of the AB42 peptide, several studies have recently found that adding the measurement of another AB peptide, the AB40 peptide, may provide a better assessment of amyloid plaque formation. Using the ratio of AB42 to AB40 levels in CSF appears to provide a greater assessment accuracy for plaque formation.
Image: This image represents the structure of Amyloid Beta.