Differential Diagnosis of Alzheimer Disease With Cerebrospinal Fluid Levels of Tau Protein Phosphorylated at Threonine 231

Büerger, Katharina; Zinkowski, Raymond; Teipel, Stefan J.; Tapiola, Tero; Arai, Hiroyuki; Blennow, Kaj; Andreasen, Niels; Hofmann-Kiefer, Klaus; DeBernardis, John F.; Kerkman, Daniel J.; McCulloch, Cheryl; Kohnken, Russell E.; Padberg, Frank; Pirttilä, Tuula; Schapiro, M. B.; Rapoport, Stanley I.; Möller, Hans; Davies, Peter; Hampel, Harald

doi:10.1001/archneur.59.8.1267

Cited by 241 publications

(165 citation statements)

References 27 publications

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“…Moreover, cognitive decline is correlated with CSF increasing levels of P-tau, these CSF tau species might specifically mark a cerebral degenerative process (Maccioni, Lavados et al 2006;Wallin, Blennow et al 2006). While other P-tau species have been measured, only CSF levels of tau proteins phosphorylated at serine 181 (P-tau 181 ) or threonine 231 (P-tau 231 ) seem to clearly improve the accuracy of the diagnostic of AD (Buerger, Zinkowski et al 2002;Hampel and Teipel 2004;Mitchell 2009). Some phosphorylations are more specific for AD, CSF P-tau 181 significantly increases in AD patients compared to patients without neurodegenerative processes as well as patients with other neurodegenerative dementias (Vanmechelen, Vanderstichele et al 2000;Vanderstichele, De Vreese et al 2006).…”

Section: Which Csf Biochemical Markers Might Allow Us To Detect Alzhementioning

confidence: 99%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Section: Which Csf Biochemical Markers Might Allow Us To Detect Alzhementioning

confidence: 99%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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“…61 The 20 largest studies 14,20,24,41,50,56,[62][63][64][65][66][67][68][69][70][71][72][73][74][75] including more than 2000 AD patients and 1000 controls, evaluating the most commonly used ELISA method for T-tau in CSF, 14 are summarized in Table 2. The mean sensitivity to discriminate AD from nondemented aged individuals has been 81%, at a specificity level of 91% (Table 2).…”

Section: Csf T-taumentioning

confidence: 99%

“…Normal CSF levels of P-tau are found in psychiatric disorders such as depression, 14,96 in chronic neurological disorders such as amyotrophic lateral sclerosis and PD, 14,52,70 and also in other most cases with other dementia disorders such as VAD, FTD, and LBD. 21,52,70,71,86,92,93 Furthermore, although there is a very marked increase in CSF T-tau in CJD, most patients with CJD have normal or only mildly elevated CSF P-tau. 26 In a large set of patients with CJD cases and other dementias, the ratio of P-tau to T-tau in CSF was found to discriminate CJD from other neurodegenerative disorders without any overlap.…”

Section: Csf P-taumentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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“…The study revealed that each of the three p-tau markers is significantly elevated in AD compared with the other groups, while p-tau231 provides the greatest discrimination between AD and other neurological disorders, and the combination of all three does not augment the discrimination [61,62] . Similarly, several other studies have revealed that p-tau231 and p-tau199 can discriminate AD from other dementias with sensitivities and specificities in the range of 80-90% [63][64][65] . It is worth noting that, as a microtubule-associated protein, hyperphosphorylation of neurofilaments potentially differentiates AD from both normal aging and other dementias [66] .…”

Section: Csf T-tau and P-tau As Biomarkers Of Admentioning

confidence: 63%

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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Differential Diagnosis of Alzheimer Disease With Cerebrospinal Fluid Levels of Tau Protein Phosphorylated at Threonine 231

Abstract: Increased levels of CSF p-tau(231) may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.

Cited by 241 publications

References 27 publications

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Cerebrospinal fluid biomarkers of Alzheimer’s disease

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