CSF tau correlates with CJD disease severity and cognitive decline

Cohen, Oren S.; Chapman, Joab; Korczyn, Amos D.; Warman-Alaluf, Naama; Nitsan, Zeev; Appel, Shmuel; Kahana, Esther; Rosenmann, Hanna

doi:10.1111/ane.12441

Cited by 25 publications

(20 citation statements)

References 38 publications

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“…This would also be in agreement with the reported correlation between CJD tau levels and the degree of cognitive impairment and disease severity as suggested recently in a study from Israel [28]. …”

Section: Discussionsupporting

confidence: 93%

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

Llorens

Karch

Golanska

et al. 2017

Dement Geriatr Cogn Disord

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Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. Results: The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (p < 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (p < 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. Conclusion: The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker.

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Section: Discussionsupporting

confidence: 93%

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

Llorens

Karch

Golanska

et al. 2017

Dement Geriatr Cogn Disord

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“…Third, unlike measures of β-amyloid that are relatively selective for AD, markers of neuronal injury are sensitive to multiple conditions. Smaller HCV is for instance also a feature of hippocampal sclerosis (Jack et al, 2002), TDP-43 proteinopathy (Whitwell et al, 2010), and argyrophilic grain disease, whereas elevated CSF tau is seen in cerebrovascular disease, Creutzfeldt-Jakob disease (Cohen et al, 2016), and traumatic brain injury (Tsitsopoulos and Marklund, 2013). Another reason for lower concordance between neuronal injury markers could be the heterogeneity between p-tau 181 and p-tau 231 , as a recent study suggests that the latter is superior in identifying AD (Spiegel et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers

Vos

Gordon

et al. 2016

Neurobiology of Aging

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The National Institute of Aging and Alzheimer’s Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and PET imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural MRI) with longitudinal clinical follow-up. Participants were classified in preclinical AD Stage 1 (β-amyloidosis) or preclinical AD Stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer pathophysiology group (SNAP; neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based upon neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in Stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury, and has important implications for clinical trials utilizing biomarkers for enrollment or as surrogate endpoint measures.

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“…[25] , S100β [26] or neuronspecific enolase [27] have been evaluated to be supportable biomarkers for CJD, but we did not include those results because it was not yet become the routine test for CJD. An additional limitation is that this study was retrospective, being based on clinical chart records from a single center in Korea.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Stages of Sporadic Creutzfeldt-Jakob Disease with Met/Met Genotype in Korean Patients

et al. 2016

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Background: Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. Methods: We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. Results: In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in <30% of patients. With progression toward stage 3, DWI hyperintensities in the subcortical nucleus increased, with a sustained higher rate of hyperintensities in the limbic and neocortical regions. With gradual progression to stage 4, the sensitivity of CSF 14-3-3 protein testing and EEG decreased and increased, respectively within limited data. Conclusions: Understanding disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis.

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CSF tau correlates with CJD disease severity and cognitive decline

Abstract: The correlation between tau levels and the disease severity and degree of cognitive decline in patients with fCJD suggests that tau can be a biomarker reflecting the extent of neuronal damage.

Cited by 25 publications

References 38 publications

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers

The Clinical Stages of Sporadic Creutzfeldt-Jakob Disease with Met/Met Genotype in Korean Patients

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