O2‐05‐04: Plasma Ptau181 Levels Reflect [18f]av1451 Tau Pet Uptake Across the Tauopathy Spectrum
Year: 2019
Type: article
Study design: Observational Study
Abstract: Biomarkers that differentiate Alzheimer's disease (AD) from other tauopathies, and quantify tau pathology are urgently needed. Blood-based assays are easier to deploy and less expensive than CSF or molecular imaging (PET) measurements. Increasing evidence suggests that plasma phospho-tau (pTau) could be a marker of tau pathology. We aimed to determine the value of plasma pTau181 for diagnosis of AD, compared to different subtypes of frontotemporal lobar degeneration (FTLD), and whether plasma pTau181 measures correlate with Tau PET imaging. Plasma pTau181 concentrations were measured in 270 individuals. Plasma pTau181 measurements were performed using a custom Meso Scale Discovery assay at Eli Lilly as previously described (Mielke et al., 2018). A subset of participants had amyloid [11C]PiB and/or [18F]AV1451 (flortaucipir [FTP]) tau PET data. PiB PET status was compared with plasma pTau181 in ROC analyses. Mean cortical [18F]FTP SUVRs were correlated with plasma pTau181 levels and voxelwise correlations identified regions where FTP-SUVR correlated with plasma pTau181. Mean plasma pTau181 concentrations were higher in AD patients (9.1±4.8 pg/ml, p<0.01) than in age matched controls (3.1±2.8 pg/ml), MCI (5.0±3.4 pg/ml), CBD (3.2±2.5 pg/ml), PSP (3.2±2.7 pg/ml), and FTLD (3.0±2.9 pg/ml). Plasma pTau181 accurately differentiated between amyloid PET positive and negative cases (ROC AUC= 0.910, p<0.0001, N=167). Plasma pTau181 concentrations were correlated with global cortical [18F]FTP uptake (Spearman's rho=0.74), with the strongest regional correlations in the lateral temporal lobes (p<1x10). Preliminary analyses in symptomatic MAPT mutation carriers (N=20) demonstrated higher plasma pTau181 levels in individuals with mutations that produce AD-like mixed 3R/4R (eg. R406W) tau, and are known to show elevated [18F]FTP uptake (Jones et al, 2018), as compared to 4R tau producing mutations (eg. N279K), that do not display [18F]FTP uptake. Plasma pTau181 concentrations are elevated in AD and MCI-AD cases as compared to age matched controls and FTLD patients. Plasma pTau181 accurately classifies patients by amyloid PET status and correlates with cortical [18F]FTP uptake in both AD and non-AD tauopathies. This suggests that plasma pTau181 reflects the level of insoluble 3R/4R tau deposition in the brain, and may be a useful diagnostic test for differentiating AD from other tauopathies and FTLD.
Source: Alzheimer s & Dementia
Authors: Elisabeth Thijssen, Julio C. Rojas, Renaud La Joie, Jeffrey Dage, David C. Airey, Nicholas Proctor, Xiyun Chai, John R. Sims, Viktoriya Bourakova, Amelia Strom, Anna M. Karydas, Ping Wang, Hilary W. Heuer, Joel H. Kramer, Bruce L. Miller, Bradley F. Boeve, Howard J. Rosen, William J. Jagust, Gil D. Rabinovici, Adam L. Boxer
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980467148