amyloid-beta-peptides and Aphasia--Primary-Progressive

To investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls.. We developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44).. The p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42.. This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation.. This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aphasia, Primary Progressive; Cohort Studies; Diagnosis, Differential; Female; Frontotemporal Dementia; Humans; Immunoassay; Male; Middle Aged; Neurodegenerative Diseases; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Supranuclear Palsy, Progressive; tau Proteins; Tauopathies

We determined cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ)(1-38), Aβ(1-40), Aβ(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20).. Commercially available ELISA and electrochemiluminescence methods were applied.. High CSF p-tau and low ratios of Aβ(1-42)/Aβ(1-40) and Aβ(1-42)/Aβ(1-38), respectively, were specific for AD. CSF Aβ(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD.. This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aphasia, Primary Progressive; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Frontotemporal Dementia; Humans; Luminescence; Male; Middle Aged; Neuropsychological Tests; Peptide Fragments; Phenotype; tau Proteins