Combination assay of CSF Tau, Aβ1-40 and Aβ1-42(43) as a biochemical marker of Alzheimer's disease

Shoji, Mikio; Matsubara, Etsuro; Kanai, Mitsuyasu; Watanabe, Mitsunori; Nakamura, Tamiko; Tomidokoro, Yasushi; Shizuka, Masami; Wakabayashi, Keiji; Igeta, Yukifusa; Ikeda, Yoshio; Mizushima, Koichi; Amari, Masakuni; Ishiguro, Kimiko; Kawarabayashi, Tatsuhiko; Harigaya, Yasuo; Okamoto, Kazuko; Hirai, Shunsaku

doi:10.1016/s0022-510x(98)00122-1

Cited by 200 publications

(126 citation statements)

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“…In addition, the concentrations of severe AD patients in this study were similar to those in HC, which is not consistent with most studies on CSF Ab 1-42 published so far. [5][6][7]9,[26][27][28][29] In this individual study, increased CSF Ab 42 was also found in depression, while two other studies have found normal levels of Ab in depressed patients 7,30 Moreover, in the measurement of Ab proteins, the assay used in the study of Jensen et al was different from the assay used to quantitate Ab in the other studies. This may have influenced the concentrations measured in their study group.…”

Section: Discussionmentioning

confidence: 77%

Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment

Hampel¹,

Teipel²,

Fuchsberger³

et al. 2003

Mol Psychiatry

281

196

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Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) bamyloid 1-42 (Ab 1-42 ) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Ab 1-42 and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Ab 1-42 and CSF tau. The levels of CSF tau were increased, whereas levels of Ab 1-42 were decreased in MCI subjects. Ab 1-42 predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Ab 1-42 , but not other predictor variables (tau protein, gender, age, apolipoprotein E e4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (Po0.05). Our findings support the notion that CSF tau and Ab 1-42 may be useful biomarkers in the early identification of AD in MCI subjects.

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Section: Discussionmentioning

confidence: 77%

Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment

Hampel¹,

Teipel²,

Fuchsberger³

et al. 2003

Mol Psychiatry

281

196

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“…Shoji et al demonstrated that combination of t-tau and Aβ42 has a sensitivity of 69% and a specifi city of 88% in the diagnosis of AD [55] . Shaw et al revealed that the combination of Aβ42, t-tau, and the number of apolipoprotein E4 alleles discriminates mild AD from MCI and healthy controls with a sensitivity of 98.2% and a specifi city of 89.9% [67] .…”

Section: Biomarkers Of Admentioning

confidence: 99%

“…Since the level of Aβ42 can be used to predict disease progression from MCI to AD [54] , it may be an early biomarker of AD. In addition, as an internal standard, Aβ40 augments the specifi city and sensitivity of Aβ42 [55] . …”

mentioning

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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“…Since CSF levels of the shorter Aβ40 isoform are unchanged or increased in AD, it has been proposed that measurement of the Aβ42/Aβ40 ratio might be superior to Aβ42 alone (Fukuyama et al, 2000;Kanai et al, 1998;Mehta et al, 2000;Schoonenboom et al, 2005;Shoji et al, 1998), even in early stage disease (Hansson et al, 2007). It is now well established that CSF A42 or CSF Aβ42/Aβ40 in conjunction with total tau (T-tau) and phospho-tau (P-tau) that reflect the axonal degeneration in AD (Ballatore et al, 2007) The discovery of shorter Aβ isoforms in brain and CSF has made it clear that Aβ constitutes a large family of peptides with considerable length variations (Portelius et al, 2008).…”

Section: A-related Proteins As Core Neurochemical Markers Of Admentioning

confidence: 99%