Improved discrimination of AD patients using β-amyloid
            <sub>(1-42)</sub>
            and tau levels in CSF

Hulstaert, Frank; Blennow, Kaj; Ivanoiu, Adrian; Schoonderwaldt, HC; Riemenschneider, Matthias; Deyn, PP De; Bancher, C.; Cras, Patrick; Wiltfang, Jens; Mehta, P. D.; Iqbal, Khalid; Pottel, Hans; Vanmechelen, Eugeen; Vanderstichele, Hugo

doi:10.1212/wnl.52.8.1555

Cited by 679 publications

(557 citation statements)

References 32 publications

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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%

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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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Section: Csf T-taumentioning

confidence: 99%

“…Also in this early phase of the disease, the sensitivity figures have been similar to those found in more advanced AD cases. 20,49,65,67,[103][104][105] …”

Section: Early Admentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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“…4 CSF-tau as a marker for neurodegeneration has already been well studied in patients with disorders such as Alzheimer's disease, stroke, and Creutzfeldt-Jakob disease. [5][6][7] We therefore carried out a pilot study to determine whether CSF-tau could be useful to monitor chemotherapy-related neurotoxicity in children being treated for hematological malignancies.…”

Section: Introductionmentioning

confidence: 99%

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies

et al. 2000

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Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. A sandwich-type ELISA (INNOTEST hTAU-Ag) was used for measuring CSF-tau. Sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic CNS invasion, already showed high CSF-tau levels at baseline (Ͼ300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS + AML. The clinical implications of both observations will be the subject of further study. Leukemia

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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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Improved discrimination of AD patients using β-amyloid _(1-42) and tau levels in CSF

Abstract: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.

Cited by 679 publications

References 32 publications

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies

Cerebrospinal fluid biomarkers of Alzheimer’s disease

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Improved discrimination of AD patients using β-amyloid (1-42) and tau levels in CSF

Abstract: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.

Cited by 679 publications

References 32 publications

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies

Cerebrospinal fluid biomarkers of Alzheimer’s disease

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Product

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Improved discrimination of AD patients using β-amyloid _(1-42) and tau levels in CSF