Analytical and Clinical Validation of β-Amyloid 1-40, 1-42, and the 1-42/1-40 Ratio using a Clinical Autoanalyzer

Alzheimer’s Disease (AD) is the predominant form of dementia in aging populations, with an estimated 6.7 million people diagnosed in the US and an annual death rate of 122,000. One of the diagnostic hallmarks of AD is extracellular deposits of β-amyloid plaques in the cortex and limbic brain region where the major molecular components of β-amyloid plaques is βamyloid 1-42 (Aβ42). Reduced concentrations of Aβ42 in cerebrospinal fluid (CSF) and plasma are associated with increased retention of Aβ tracers in the brain β-amyloid plaques observed with positron emission tomography (PET). Correlation to PET results is further improved by using the ratio of Aβ42 to βamyloid 1-40 (Aβ40) to account for variation in total β-amyloid from person-to-person. Although PET imaging and measurements in CSF have been traditionally used to investigate the presence of β-amyloid plaques, these techniques are invasive to the patient. To provide an alternative, the Sysmex HISCL®-5000 Immunoassay System was used to validate chemiluminescence enzyme immunoassays for the measurement of Aβ40 and Aβ42 in EDTA plasma samples as a laboratory developed test (LDT) to determine the Aβ42/40 ratio.