Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

Park, Jong Chan; Han, Sun Ho; Cho, Hyun Jin; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Kang, Seok Seon; Jung, Eun Sun; Won, Su Jin; Kim, Eun Hye; Kim, Yu Kyeong; Lee, Dong Hoon; Mook‐Jung, Inhee

doi:10.1186/s13195-017-0248-8

Cited by 58 publications

(64 citation statements)

References 56 publications

(61 reference statements)

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“…We validated the diagnostic accuracy of this diagnostic kit in a clinical trial with a 300-person validation cohort of individuals who were imaged using PiB-PET. In the previous discovery stage, we utilized ELISA to detect LGALS3BP, ACE, and POSTN, and used xMAP to detect A 1-40; with this strategy, we used the developed kit to validate that there were differences in the blood levels of the four biomarkers between the PiB− and PiB+ groups (3,4). In the QPLEX TM Alz plus assay kit, we simultaneously detected LGALS3BP, ACE, POSTN, and A 1-40 using QMAP technology, which helped maximize the detection e ciency for low-abundance blood proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Although direct brain-imaging methods using A -speci c positron emission tomography (PET) ligands have been developed, such as Pittsburgh compound B (PiB) and orbetapir (1), PET is not an easily accessible method because of its high cost and radiation exposure. Especially in the early stages of the disease, when pathological hallmarks exist in the brain but no clinical symptom is seen, patients would be unlikely to undergo a brain PET scan (2,3). This a major obstacle when early diagnosis relies on PET.…”

Section: Introductionmentioning

confidence: 99%

“…In a previous study, we revealed a novel blood-based biomarker panel for cerebral amyloid deposition consisting of galectin-3 binding protein (LGALS3BP), A 1-40, angiotensin converting enzyme (ACE), and periostin (POSTN) (3,4). When assessed by logistic regression analysis and receiver operating characteristic (ROC) curve analysis, our biomarker panel exhibited a high area under the curve (AUC) and good sensitivity and speci city when blood levels were quanti ed through commercialized enzyme-linked immunosorbent assay (ELISA) kits or the xMAP technology.…”

Section: Introductionmentioning

confidence: 99%

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Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

Park

Jung²,

Kim³

et al. 2020

Preprint

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Background: Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial. Methods: We developed a new multiplex kit, the QPLEXTM Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEXTM biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method.Results: The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEXTM Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%.Conclusions: Our QPLEXTM Alz plus assay kit offers a highly effective way to predict cerebral amyloid deposition through a convenient blood test, and should enable easy prediction of AD in daily life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

Park

Jung²,

Kim³

et al. 2020

Preprint

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“…Plasma Aβ 1−42 showed a positive relationship in our model for CSF Aβ 1−42 , in line with a prior observation 43 . This is interesting, as the link between alterations of Aβ 1−42 levels in the blood and the progression of the disease is still controversial and studies assessing the Aβ 1−42 concentration in blood of AD patients have produced conflicting results [43][44][45][46][47][48][49] . Chromogranin A (CGA) is associated with synaptic function, and has traditionally been used as an indicator of neuroendocrine tumors 50 .…”

Section: Discussionmentioning

confidence: 99%

A blood-based signature of cerebrospinal fluid Aβ_1–42status

Goudey

Fung

Schieber

et al. 2017

Preprint

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It is increasingly recognized that Alzheimer's disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebral spinal fluid (CSF) amyloid β 1−42 (Aβ 1−42 ) may be an earlier indicator of Alzheimer's disease risk than measures of amyloid obtained from Positron Emission Topography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap.In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual's CSF amyloid status. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ 1−42 levels indicative of AD risk (0.84 AUC, 0.73 sensitivity, and 0.76 specificity). Post-hoc analysis indicates that only six analytes are required to achieve similar performance. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ 1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those predicted with normal CSF Aβ 1−42 levels. This is the first study to show that a plasma protein signature, together with age and APOE 4 genotype, is able to predict CSF Aβ 1−42 levels with high accuracy. Biomarkers in plasma have previously been shown to be predictive of PET amyloid levels. This work further highlights the potential for developing a blood-based signature for improved AD screening, critical for drug and intervention trials.

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“…It is widely accepted that increased production and accumulation of β‐amyloid peptide (Aβ) is observed in mild cognitive impairment (MCI) which is the early stage of AD progression . Evidences have shown that cerebral deposition of Aβ could be detected in both MCI and AD patients . In recent studies, it has been reported that cholesterol‐oxygenated derivatives (oxysterols) play a remarkable role in the onset and progression of memory loss and cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

Zhang

et al. 2019

Brain Pathology

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The oxysterol 27-hydroxycholesterol (27-OHC) has been considered to play a key role in the pathogenesis of Alzheimer's disease (AD). Because β-amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27-OHC could lead to cognitive impairment through modulating Aβ accumulation and deposition. Regulation of Aβ metabolism was explored as the pathogenic mechanism of 27-OHC. Furthermore, microRNAs (miRNAs) and their relations with 27-OHC were also detected. In present study, matched case-control study and APP/PS1 transgenic mice research were conducted. The results showed that the 27-OHC and Aβ in plasma were increased in mild cognitive impairment patients, and a slight correlation was found between 27-OHC and Aβ1-40. This relationship was also proved by the research of APP/PS1 mice. More severe learning and memory impairment and higher Aβ1-40 expression in brain and plasma were detected in the APP/PS1 mice of 27-OHC treatment group. In addition, increased amyloid plaques were also found in the hippocampus of 27-OHC-treated mice. In order to find out the mechanism of 27-OHC on regulating Aβ metabolism, the factors of Aβ production (APP, BACE1 and ADAM10), transport (LRP1 and RAGE) and elimination (NEP and IDE) were tested respectively. The gene and protein expressions of APP, BACE1 and RAGE were increased while LRP1 and IDE were decreased in the brain of 27-OHC-treated mice. At last, down-regulated expression of miRNA let-7g-5p was found after 27-OHC treatment. In conclusion, these findings suggested that excessive 27-OHC could enhance the accumulation and deposition of Aβ both in brain and blood, resulting in a severe impairment of cognition, especially in the modulation of Aβ1-40. The mechanism might be associated with the regulation of Aβ metabolism, and miRNA let-7g-5p was likely to play a vital role in this pathological process induced by 27-OHC.Brain Pathology 29 (2019) 558-573

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Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

Cited by 58 publications

References 56 publications

Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

A blood-based signature of cerebrospinal fluid Aβ_1–42status

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

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Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition

Cited by 58 publications

References 56 publications

Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

Performance of the QPLEXTM Alz Plus Assay, A Novel Multiplex Kit for Screening Cerebral Amyloid Deposition

A blood-based signature of cerebrospinal fluid Aβ1–42status

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

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A blood-based signature of cerebrospinal fluid Aβ_1–42status