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O3‐14‐03: IDENTIFICATION OF NOVEL CEREBROSPINAL FLUID BIOMARKER CANDIDATES FOR DEMENTIA WITH LEWY BODIES: A PROTEOMIC APPROACH
Author(s) -
Steenoven Inger,
koel-Simmelink Marleen J.A.,
Vergouw Leonie J.M.,
Piersma Sander R.,
Pham Thang V.,
Flier Wiesje M.,
Jan de Jong Frank,
Jimenez Connie R.,
Lemstra Afina W.,
Teunissen Charlotte E.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2851
Subject(s) - biomarker , dementia with lewy bodies , proteomics , cohort , cerebrospinal fluid , dementia , medicine , disease , oncology , pathology , bioinformatics , biology , genetics , gene
Paired phosphorylated and unphosphorylated peptides at sites T181, S202, T205 and T217 were quantified. Relationships between tau phosphorylation and [F]GTP1 SUVRwere assessed using Spearman correlation analysis. The false discovery rate (FDR) for ROI-level correlation analyses was controlled using the Benjamini-Hochberg procedure. Results: [F]GTP1 SUVR and CSF tau phosphorylation increase with disease severity (expressed as the ratio of phosphorylated to unphosphorylated peptides). Spearman correlation analysis reveals that in n1⁄438 individuals T217 (r1⁄40.69) and T205 (r1⁄40.55) are more correlated with [F]GTP1 (whole-cortical gray) SUVR than T181 (r1⁄40.28). Correlations strengthen when using a more specific AD-meta ROI (Jack et al., 2017) to calculate [F]GTP1 SUVR, with T217 having the strongest correlation (r1⁄40.81) (T205, r1⁄40.63, T181 r1⁄40.35). Preliminary comparisons of different regional analyses of [F]GTP1, and relationships with cognitive endpoints may also be presented. Conclusions:These results provide insight into the relationship between tau PET imaging and CSF phospho-tau, and may help guide the usage and interpretation of biomarker data in the clinic. CSF species containing phosphosites T217 and T205 may be more closely reflective of tauopathy, as detected by tau PET.