Plasma Levels of Aβ42 and Tau Identified Probable Alzheimer’s Dementia: Findings in Two Cohorts

Lue, Lih‐Fen; Sabbagh, Marwan N.; Chiu, Ming‐Jang; Jing, Naomi Y; Snyder, Noelle; Schmitz, Christopher T.; Guerra, André; Belden, Christine M.; Chen, Ta‐Fu; Yang, Chung-Hsin; Yang, Shieh‐Yueh; Walker, Douglas G.; Chen, Kewei; Reiman, Eric M.

doi:10.3389/fnagi.2017.00226

Cited by 89 publications

(107 citation statements)

References 54 publications

(83 reference statements)

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“…The application of noninvasive blood-based biomarkers for diagnosing and tracking AD by specific biomarkers such as Aβ 1-40 , Aβ 1-42 , and T-tau has been reported in the past 10 years [26,27]. Many studies showed that the plasma biomarkers may help for screening of AD patients [28][29][30]. In clinical studies, retrospective plasma samples are frequently used, which might experience freeze/thaw cycles before assays of biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Stability of Plasma Amyloid-β 1–40, Amyloid-β 1–42, and Total Tau Protein over Repeated Freeze/Thaw Cycles

Liu¹,

Chiu

Lin

et al. 2020

Dement Geriatr Cogn Disord Extra

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Introduction: Blood biomarkers of Alzheimer's disease (AD) have attracted much attention of researchers in recent years. In clinical studies, repeated freeze/thaw cycles often occur and may influence the stability of biomarkers. This study aims to investigate the stability of amyloid-β 1-40 (Aβ 1-40 ), amyloid-β 1-42 (Aβ 1-42 ), and total tau protein (T-tau) in plasma over freeze/thaw cycles. Methods: Plasma samples from healthy controls (n = 2), AD patients (AD, n = 3) and Parkinson's disease patients (PD, n = 3) were collected by standardized procedure and immediately frozen at -80 ° C. Samples underwent 5 freeze/thaw (-80 ° C/room temperature) cycles. The concentrations of Aβ 1-40 , Aβ 1-42 , and T-tau were monitored during the freeze/ thaw tests using an immunomagnetic reduction (IMR) assay. The relative percentage of concentrations after every freeze/thaw cycle was calculated for each biomarker. Results: A tendency of decrease in the averaged relative percentages over samples through the freeze and thaw cycles for Aβ 1-40 (100 to 97.11%), Aβ 1-42 (100 to 94.99%), and T-tau (100 to 95.65%) was found. However, the decreases were less than 6%. For all three biomarkers, no statistical significance was found between the levels of fresh plasma and those of the plasma experiencing 5 freeze/thaw cycles (p > 0.1). Conclusions: Plasma Aβ 1-40 , Aβ 1-42 , and T-tau are stable through 5 freeze/thaw cycles measured with IMR.

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Section: Discussionmentioning

confidence: 99%

Stability of Plasma Amyloid-β 1–40, Amyloid-β 1–42, and Total Tau Protein over Repeated Freeze/Thaw Cycles

Liu¹,

Chiu

Lin

et al. 2020

Dement Geriatr Cogn Disord Extra

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“…The Aβ 42 /Aβ 40 ratio improves the diagnostic power of the plasma Aβ biomarkers [58], and plasma Aβ 42 correlates with CSF Aβ 42 in AD [59]. Additional researches indicated that plasma Aβ 42 and tau can be used to assist in the clinical diagnosis of AD [60], and the concentration of P-tau181 in plasma can be used to differentiate memory disorder/cognitive decline in early-stage AD patients [61]. Clearly, these ultrahigh-sensitive assay technologies provide novel methods to measure low-level proteins especially in blood.…”

Section: Blood-based Biomarkermentioning

confidence: 99%

“…Using the SQUID-based IMR, the low detection limit for amyloids and tau protein is found to be 1-10 pg/mL [57,58]. Thus, it makes possible the measurement of plasma biomarkers for the diagnosis of AD [58][59][60][61]. For example, by IMR technology, the previous studies suggested that the plasma Aβ 42 is a useful biomarker for AD.…”

Section: Blood-based Biomarkermentioning

confidence: 99%

Precision Medicine: Role of Biomarkers in Early Prediction and Diagnosis of Alzheimer’s Disease

Shen¹,

Xia²,

Zhang³

et al. 2019

Molecular Medicine

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Alzheimer's disease (AD), the most common form of dementia in the aged people, is a chronic and irreversible neurodegenerative disorder. Early prediction, intervention, and objective diagnosis are very critical in AD. In this chapter, we will introduce the current progress in the prediction and diagnosis of AD, including recent development in diagnostic criteria, genetic testing, neuroimaging techniques, and neurochemical assays. Focus will be on some new applied methods with more specific examples, that is, cerebrospinal fluid (CSF) and blood proteins and peptides, which might serve as biomarkers for the diagnosis of AD. We will also discuss biomarker-based diagnostic strategies and their practical application.

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“…The method involves conjugation of an anti-Aβ antibody to magnetic particles, whereafter a change in the IMR upon addition of plasma and binding of Aβ42 to the antibodies can be sensed (Yang et al, 2011). Using the technique, an increase in plasma Aβ42 signal has been observed (Lue et al, 2017;Teunissen et al, 2018), i.e., a result that goes opposite to the mass spectrometry-based methods. One potential explanation for this result is that the technique might detect some sort of Aβ aggregate or Aβ bound to other proteins and that these may be present at increased levels in AD plasma.…”

Section: Plasma Aβmentioning

confidence: 99%

Blood-based biomarkers for Alzheimer’s disease—An update

Zetterberg

2019

Journal of Neuroscience Methods

115

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Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are in clinical use in many parts of the world and show good to excellent diagnostic accuracy in regards to identifying cerebral amyloid β (Aβ) and tau pathology irrespective of the clinical stage of the disease. However, CSF sampling is more difficult than a blood draw and a procedure only rarely performed by general practitioners. Since AD is such a common disease and since intense research on novel treatments that hopefully will be directed against underlying pathologies is moving forward, it would be excellent if the CSF tests for AD could be transformed into blood tests, as well as if novel blood biomarkers could be discovered. Brainderived molecules are, however, present at much lower concentrations in blood than in CSF, which poses an analytical challenge. There are also additional issues with blood as a biofluid in which to measure biomarkers for central nervous system disease. Nevertheless, the past few years have seen an enormous development in the field of ultrasensitive measurement techniques. There is also much better availability of deeply phenotyped clinical cohorts for biomarker discovery and validation. This review gives an updated account of the current state of research on blood biomarkers for AD and related neurodegenerative dementias with special emphasis on findings that have been replicated by more than one research group.

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Plasma Levels of Aβ42 and Tau Identified Probable Alzheimer’s Dementia: Findings in Two Cohorts

Cited by 89 publications

References 54 publications

Stability of Plasma Amyloid-β 1–40, Amyloid-β 1–42, and Total Tau Protein over Repeated Freeze/Thaw Cycles

Stability of Plasma Amyloid-β 1–40, Amyloid-β 1–42, and Total Tau Protein over Repeated Freeze/Thaw Cycles

Precision Medicine: Role of Biomarkers in Early Prediction and Diagnosis of Alzheimer’s Disease

Blood-based biomarkers for Alzheimer’s disease—An update

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