Plasma Aβ42/40 Ratio Detects Early Stages of Alzheimer’s Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study

V. Pérez-Grijalba, J. Romero, Pedro Pesini, L. Sarasa, I. Monleón, I. San-José, J. Arbizu, P. Martínez-Lage, J. Munuera, A. Ruiz, L. Tárraga, M. Boada, M. Sarasa

Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.