Replication study of plasma proteins relating to Alzheimer's pathology.
Shi L., Winchester LM., Westwood S., Baird AL., Anand SN., Buckley NJ., Hye A., Ashton NJ., Bos I., Vos SJB., Kate MT., Scheltens P., Teunissen CE., Vandenberghe R., Gabel S., Meersmans K., Engelborghs S., De Roeck EE., Sleegers K., Frisoni GB., Blin O., Richardson JC., Bordet R., Molinuevo JL., Rami L., Wallin A., Kettunen P., Tsolaki M., Verhey F., Lléo A., Sala I., Popp J., Peyratout G., Martinez-Lage P., Tainta M., Johannsen P., Freund-Levi Y., Frölich L., Dobricic V., Legido-Quigley C., Barkhof F., Andreasson U., Blennow K., Zetterberg H., Streffer J., Lill CM., Bertram L., Visser PJ., Kolb HC., Narayan VA., Lovestone S., Nevado-Holgado AJ.
INTRODUCTION: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. METHODS: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. RESULTS: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. DISCUSSION: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.