Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 55, Issue 4, Pages 1471-1480Publisher
IOS PRESS
DOI: 10.3233/JAD-160740
Keywords
Alzheimer's disease; amyloid-beta; biomarker; cerebrospinal fluid; Creutzfeldt-Jakob disease; prion protein; tau protein
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Funding
- Italian Ministry of Health [RF2011-02351092]
- Gino Galletti Foundation
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According to recent studies, the determination of cerebrospinal fluid (CSF) total tau (t-tau)/phosphorylated tau (p-tau) ratio and total prion protein (t-PrP) levels significantly improves the accuracy of the diagnosis of Alzheimer's disease (AD) in atypical cases with clinical or laboratory features mimicking Creutzfeldt-Jakob disease (CJD). However, this has neither been validated nor tested in series including atypical CJD variants. Furthermore, the added diagnostic value of amyloid-beta (A beta)(42) remains unclear. To address these issues, we measured t-PrP, 14-3-3, t-tau, p-tau, and A beta(42) CSF levels in 45 typical and 44 atypical/rapidly progressive AD patients, 54 typical and 54 atypical CJD patients, and 33 controls. CJD patients showed significantly lower CSF t-PrP levels than controls and AD patients. Furthermore, atypical CJD was associated with lower t-PrP levels in comparison to typical CJD. T-tau, 14-3-3, or t-PrP alone yielded, respectively, 80.6, 63.0, and 73.0% sensitivity and 75.3, 92.1, and 75% specificity in distinguishing AD from CJD. On receiver operating characteristic (ROC) curve analyses of biomarker combinations, the (t-tau x A beta(42))/(p-tau x t-PrP) ratio achieved the best accuracy, with 98.1% sensitivity and 97.7% specificity overall, and 96.2% sensitivity and 95.5% specificity for the atypical disease groups. Our results show that the combined analysis of CSF t-PrP, t-tau, p-tau, and A beta(42) is clinically useful in the differential diagnosis between CJD and AD. Furthermore, the finding of reduced CSF t-PrP levels in CJD patients suggest that, likewise A beta(42) in AD, CSF t-PrP levels reflect the extent of PrPc conversion into abnormal PrP (PrPSc) and the burden of PrPSc deposition in CJD.
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