Comparison of plasma and cerebrospinal fluid protein markers and their significance for the characterization of dementia disease status
Year: 2023
Type: article
Abstract: Background Although Aβ42 and phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) are valuable to diagnose Alzheimer’s disease (AD), many patients are reluctant to accept lumbar puncture. In addition, there is lack of biomarkers for the different stages of AD dementia. This study sought to compare the plasma and CSF protein markers to characterize dementia status. Method This cohort study included Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants who had baseline levels of 73 proteins measured in plasma (566 total, 58 cognitively normal (CN), 396 mild cognitive impairment (MCI), and 112 AD) and in CSF (310 total, 92 CN, 149 MCI, and 69 AD). Univariate/multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used to identify the protein candidates for the disease classification. The following three models were examined for CN vs. MCI and MCI vs. AD; model 1: proteins only, model 2: proteins adjusted for age, sex, education, and model 3: model 2 plus APOE4 status. Result Nine proteins in plasma and CSF were chosen based on their importance from LASSO. The area under the curve (AUC) for the final multivariate logistic regression including the 9 proteins was calculated for each disease group in plasma [CN vs. MCI: 0.895 (model 1), 0.899 (model 2), 0.921 (model 3), and MCI vs. AD: 0.828 (model 1), 0.842 (model 2), 0.856 (model 3)]. In addition, AUC in CSF [CN vs. MCI: 0.678 (model 1), 0.726 (model 2), 0.770 (model 3) and MCI vs. AD: 0.711 (model 1), 0.738 (model 2), 0.765 (model 3)] was also estimated. We observed that plasma proteins outperformed the CSF proteins to be associated with MCI and AD. Also, plasma proteins were significantly better than the established AD markers, namely CSF Aβ42 and p‐tau in CN vs. MCI [AUC: 0.836 (model 1), 0.842 (model 2), 0.862 (model 3)] and MCI vs. AD [AUC: 0.665 (model 1), 0.673 (model 2), 0.680 (model 3)]. Conclusion This study demonstrates that the combination of plasma proteins could be considered an effective marker for diagnosing AD and its early‐stage symptoms with better performance than the other markers.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.077600
Institution: Boston University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390199551