Multiplex immunoassay measurement of amyloid-β₄₂ to amyloid-β₄₀ ratio in plasma discriminates between dementia due to Alzheimer’s disease and dementia not due to Alzheimer’s disease

The cerebrospinal fluid (CSF) biomarkers amyloid-β₄₂ (Aβ₄₂), total Tau, and phospho-181-Tau represent important diagnostic tools to support the clinical diagnosis of Alzheimer’s disease (AD). Acquiring CSF by lumbar puncture is considered a moderately invasive procedure, while blood sampling is minimally invasive with calculable risks and can be performed by trained non-medical staff. Thus, the identification of reliable and robust blood biomarkers of AD-related neuropathology would be significantly advantageous in daily practice and would allow more patients to be screened. In this study, we performed a multiplex amyloid-β assay to simultaneously measure Aβ₄₀ and Aβ₄₂. We analyzed how well Aβ₄₀, Aβ₄₂, and the Aβ₄₂ to Aβ₄₀ ratio (Aβ_42/40) could differentiate between patients suffering from dementia either due or not due to AD. In addition, we studied different factors affecting Aβ levels in plasma. Plasma Aβ_42/40 level was significantly lower in patients with dementia due to AD than in those with dementia due to other causes. Aβ_42/40 correlated weakly between plasma and CSF, but did not differ between amyloid-PET positive or negative patients. Furthermore, we found that kidney function influences Aβ₄₀ and Aβ₄₂ plasma levels, but not Aβ_42/40 level. Liver function, age, and sex do not affect Aβ levels in plasma.