Presenter of 1 Presentation
INTEGRATED CEREBROSPINAL FLUID AND PLASMA PROTEOMICS REVEALS CANDIDATE PROTEINS AND NETWORK RELATING TO THE AT(N) FRAMEWORK
Abstract
Aims
The AT(N) framework has been widely used to classify Alzheimer’s disease (AD). However, the biological network and pathway relating to the AT(N) framework remain incompletely understood. The objective of this study is to perform an in depth proteomic profiling of cerebrospinal fluid (CSF) and plasma from AD patients to gain a better understanding of its pathogenesis.
Methods
We used mass spectrometry to measure 2535 proteins in CSF samples in 371 subjects (125 controls, 152 mild cognitive impairment [MCI], and 94 AD) selected from the EMIF-AD study. SOMAscan platform was used to measure 4001 proteins in plasma in 972 subjects (372 controls, 409 MCI, and 191 AD) from the same study. We firstly performed both linear regression and protein co-expression network to identify differentially expressed proteins and co-expressed protein modules associated with the AT(N) framework in CSF. We then validated such associations in plasma samples.
Results
In CSF, we identified three modules, all of which were significantly associated with the AT(N) framework. Furthermore, two of these modules were preserved in plasma proteomics and the AT(N) associations were also maintained. In addition, we identified 245 proteins in CSF that were significantly associated with the AT(N) framework after multiple correction. Of these, 21 proteins were also significantly associated with the AT(N) framework in plasma.
Conclusions
We identified both protein modules and single proteins relating to the AT(N) framework in CSF and then validated such associations in plasma. These proteins provide tractable targets for further biomarkers and mechanistic studies of Alzheimer’s pathophysiology.