Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

Kapaki, Elisabeth

doi:10.1136/jnnp.71.3.401

Cited by 125 publications

(80 citation statements)

References 14 publications

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“…to assume that there is no difference between groups despite a true difference of markers in the population. Our results, however, showing significantly lower levels of CSF p-tau 231 and t-tau in HC subjects compared to AD patients as well as extremely high t-tau values in CJD compared to other diagnostic entities are in accordance with the literature [2,3,4,7,11,15]. The main findings of our study refer to the CJD and the AD groups, i.e.…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, a biomarker to support differential diagnosis between CJD and AD would be clinically meaningful. In cerebrospinal fluid (CSF), determination of total tau protein (t-tau) concentration is of high diagnostic value for CJD with sensitivity and specificity levels above 90% when distinguishing CJD from non-demented and demented neurological controls and AD [11,15,20,21]. T-tau levels are elevated both in CJD and AD relative to controls, but the increase is several magnitudes higher in CJD compared to AD.…”

Section: Introductionmentioning

confidence: 99%

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Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Büerger

Otto

Teipel

et al. 2006

Neurobiology of Aging

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To study the potential diagnostic value of abnormally phosphorylated tau protein in Creutzfeldt-Jakob disease (CJD) compared to Alzheimer's disease (AD), we determined levels of tau phosphorylated at threonine 231 (p-tau 231 ) and of total tau (t-tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-tau levels but relatively low p-tau 231 concentrations compared to the AD group. t-tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-tau 231 and the p-tau 231 /t-tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-tau and p-tau 231 in CJD when compared to AD.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Büerger

Otto

Teipel

et al. 2006

Neurobiology of Aging

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“…As so the ratio between phosphorylated tau (p-tau) and t-tau levels (p-tau/ t-tau) was shown to improve discrimination between AD and sCJD, with lower levels in favour of the latter [5,28,32]. Reduced Ab42 CSF levels have also been reported in sCJD patients, as in AD, but mostly overlapping [17,38,39]. NSE and S-100b are elevated in sCJD patients, but do not seem to attain sufficient sensitivity and specificity for differential diagnosis [21,30,43].…”

Section: Introductionmentioning

confidence: 93%

“…Following the principle that CSF proteins reflect changes in pathological brain conditions, elevated levels of these proteins are used as surrogate markers for neuronal damage (14-3-3, tau, NSE) or astrocytic gliosis (S-100b). CSF total tau (t-tau) reaches extremely high levels in sCJD, probably reflecting the extent of the neurodegenerative process, and has been reported to be clinically useful, with sensitivity and specificity for sCJD similar to the 14-3-3 test [17,22,38,39]. Unlike what happens in Alzheimer's disease (AD), hyperphosphorylation of tau and formation of neurofibrillary tangles (NFTs) do not occur in sCJD.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

et al. 2009

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The clinical diagnosis of sporadic CreutzfeldtJakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and b amyloid (Ab42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Ab42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Ab42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

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“…Many studies demonstrated that the levels of CSF Aβ42 in AD are decreased compared with controls [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] . CSF Aβ42 can differentiate AD from controls with 89% sensitivity and 90% specificity [51] .…”

Section: Csf Aβ42 As a Biomarker Of Admentioning

confidence: 99%

Cerebrospinal fluid biomarkers of Alzheimer’s disease

Sui

Yang

2014

Neurosci. Bull.

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Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to fi nd specifi c biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and infl ammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fl uid (CSF) biomarkers (β-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identifi ed by proteomics, updated in the last fi ve years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.Keywords: Alzheimer's disease; biomarker; cerebrospinal fl uid; β-amyloid; tau; proteomics ·Review· Introduction Alzheimer's disease (AD) is becoming more prevalent due to the increasing population of people aged over 65 [1] .It is estimated that it will affect 66 million by 2030 and 115 million by 2050 worldwide if no effective therapeutic strategies are found [2] . Clinically, AD is characterized by cognitive impairment, progressive disturbance of daily activities, many neuropsychiatric symptoms, and behavioral deterioration [3][4][5][6][7][8] . Pathologically, it is characterized by deposition of extracellular neuritic plaques composed of β-amyloid (Aβ) [9] and intracellular neurofibrillary tangles (NFTs) consisting of a hyperphosphorylated form of the microtubule-associated protein tau [10][11][12] . Besides, loss of neurons and synapses is also a pathological hallmark of AD [13][14][15] . The worldwide cost of dementia is huge and expected to skyrocket in the next few years. AD may become one of the most marked social, health, and economic challenges in the twenty-fi rst century [16] .Clinically, the procedure for the diagnosis of AD is diffi cult and complex. Neuropsychological tests, such as the mini-mental state examination, magnetic resonance imaging of hippocampal volume, and clinical assessment, are used to aid in diagnosis. However, a defi nitive diagnosis of AD requires confirmation at autopsy. It is estimated to take 8-10 years or longer before mild cognitive impairment (MCI) develops into AD [17,18] . Meanwhile, intervention therapies work most effectively in the early stage of AD. Thus, it is urgent and feasible to seek novel specifi c biomarkers to aid in diagnosis and the evaluation of treatments [19] . Surrounding the brain and spinal cord, cerebrospinal fluid (CSF) is an ideal source refl ecting biochemical changes in the brain of the AD patient [20] . Extensive studies have focused on seeking AD biomarkers in CSF.A comprehensive search of the Web of Science (Janua...

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Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

Cited by 125 publications

References 14 publications

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

Cerebrospinal fluid biomarkers of Alzheimer’s disease

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