Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan

Kanai, Mitsuyasu; Matsubara, Etsuro; Isoe, Kenji; Urakami, Katsuya; Nakashima, Kenichiro; Arai, Hiroyuki; Sasaki, Hidetada; Abe, Kōji; Iwatsubo, Takeshi; Kosaka, Toshiyuki; Watanabe, Mitsunori; Tomidokoro, Yasushi; Shizuka, Masami; Mizushima, Koichi; Nakamura, Tamiko; Igeta, Yukifusa; Ikeda, Yoshio; Amari, Masakuni; Kawarabayashi, Tatsuhiko; Ishiguro, Koichi; Harigaya, Yasuo; Wakabayashi, Keiji; Okamoto, Koichi; Hirai, Shunsaku; Shoji, Mikio

doi:10.1002/ana.410440108

Cited by 328 publications

(227 citation statements)

References 49 publications

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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: 78%

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

282

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: 78%

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

282

196

View full text Add to dashboard Cite

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“…Sandwich ELISA was used to quantify plasma A β x‐40 and A β x‐42 levels using a Human/Rat β Amyloid (40) ELISA Kit Wako II and a Human/Rat β Amyloid (42) ELISA Kit Wako High‐Sensitive (Wako Pure Chemical Industries, Ltd, Osaka, Japan) 22, 23. Microplates were precoated with monoclonal BNT77 (IgA, anti‐A β 11‐28, specific for A β 11‐16) and sequentially incubated with 25 μ L of samples, followed by application of horseradish‐peroxidase‐conjugated BA27 (anti‐A β 1‐40, specific for A β 40) or BC05 (anti‐A β 35‐43, specific for A β 42/43).…”

Section: Methodsmentioning

confidence: 99%

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

Nakamura

Kawarabayashi

Seino

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe aim of this study was to confirm determinative factors for plasma Aβ and its association with cognitive function.MethodsFasting plasma Aβ40 and Aβ42 levels were measured by ELISA in 1019 participants in the Iwaki Health Promotion Project. The relationships between plasma Aβ and health‐related items, including physical characteristics, cognitive function tests, blood chemistry, and APOE‐ε4 genotype were analyzed.ResultsThe plasma levels of Aβ40 and Aβ42, and Aβ40/42 ratio were found to significantly increase with aging. The age‐dependent increase in Aβ42 level was significantly suppressed by APOE‐ε4. Renal function was an associated factor for the plasma Aβ40 level. The plasma Aβ42 level and Aβ40/42 ratio correlated with cognitive function.InterpretationAge and APOE‐ε4 are major determinative factors of plasma levels of Aβ42 and the Aβ40/42 ratio. These factors are critical adjustment factors for the usage of plasma Aβ as a biomarker of central nervous system amyloidosis.

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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%

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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Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan

Cited by 328 publications

References 49 publications

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

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

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

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