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. 2018;65(4):1417-1425.
doi: 10.3233/JAD-180548.

Clinical Experience with Cerebrospinal Fluid Aβ42, Total and Phosphorylated Tau in the Evaluation of 1,016 Individuals for Suspected Dementia

Leonardo Tariciotti  1 , Matthew Casadei  2 , Lawrence S Honig  3   4 , Andrew F Teich  3   5 , Guy M McKhann Ii  6 , Giuseppe Tosto  3   7   4 , Richard Mayeux  3   7   4   8
Affiliations

Clinical Experience with Cerebrospinal Fluid Aβ42, Total and Phosphorylated Tau in the Evaluation of 1,016 Individuals for Suspected Dementia

Leonardo Tariciotti et al. J Alzheimers Dis. 2018.

Abstract

Background: Elevated total tau (tTau), 181-phosphorylated phosphorylated tau (pTau), and low amyloid-β42 (Aβ42) in cerebrospinal fluid (CSF) represent a diagnostic biomarker for Alzheimer's disease (AD).

Objective: The goal was to determine the overall accuracy of CSF Aβ42, tTau, pTau, and the Aβ42/total tau index (ATI) in a non-research, clinical setting for the diagnosis of AD.

Methods: From medical records in 1,016 patients that had CSF studies for dementia over a 12-year period (2005 to 2017), we calculated the sensitivity and specificity of CSF Aβ42, tTau, and pTau and the ATI in relation to the final clinical diagnosis.

Results: Compared with non-demented patients and patients with other dementias or mild cognitive impairment (MCI), the sensitivity and specificity of the recommended ATI and pTau cut-offs (ATI < 1.0 and pTau >61 pg/ml) for the diagnosis of AD were 0.88 and 0.72, respectively. Similar results were obtained comparing AD with non-demented patients only (0.88, 0.82) and AD with other types of dementia (0.81, 0.77). A subgroup of patients with presumed normal pressure hydrocephalus (n = 154) were biopsied at the time of shunt placement. Using the pathological manifestations of AD as the standard, the sensitivity was 0.83 while the specificity was 0.72.

Conclusions: In a non-research setting, CSF biomarkers for AD showed a high sensitivity in accordance with previous studies, but modest specificity differentiating AD from other types of dementia or MCI. This study of unselected patients provides a valid and realistic assessment of the diagnostic accuracy of these CSF biomarkers in clinical practice.

Keywords: Alzheimer’s disease; Aβ42; CSF biomarkers; accuracy; pTau; sensitivity; specificity; tTau.

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Figures

Fig.1
Fig.1
Receiver operation curve (ROC). Alzheimer’s disease compared to overall population of the cohort. Alzheimer’s disease (n = 264) was compared to the overall population of the cohort (n = 752). Aβ42 (red), tTau (green), pTau (blue), and ATI (black) CSF biomarker ROC curves are reported here. AUC analyses fully reported in the text.
See this image and copyright information in PMC

References

    1. Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Aβ42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60, 652–656. - PubMed
    1. Tapiola T, Alafuzoff I, Herukka S, Parkkinen L, Hartikainen P, Soininen H, Pirttilä T (2009) Cerebrospinal fluid β-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66, 382–389. - PubMed
    1. Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, LaRossa GN, Spinner ML, Klunk WE, Mathis CA, DeKosky ST, Morris JC, Holtzman DM (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42in humans. Ann Neurol 59, 512–519. - PubMed
    1. Tolboom N, van der Flier WM, Yaqub M, Boellaard R, Verwey NA, Blankenstein MA, Windhorst AD, Scheltens P, Lammertsma AA, van Berckel BNM (2009) Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. J Nucl Med 50, 1464–1470. - PubMed
    1. Mattsson N, Insel PS, Landau S, Jagust W, Donohue M, Shaw LM, Trojanowski JQ, Zetterberg H, Blennow K, Weiner M (2014) Diagnostic accuracy of CSF Aβ42 and florbetapir PET for Alzheimer’s disease. Ann Clin Transl Neurol 1, 534–543. - PMC - PubMed

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