Plasma amyloid-β oligomers level is a biomarker for Alzheimer’s disease diagnosis

Zhou, Ling; Chan, Koon‐Ho; Chu, Leung Wing; Kwan, Jason Shing-Cheong; Song, You‐Qiang; Chen, L.H.; Ho, Philip Wing-Lok; Cheng, On-Yin; Ho, J.C.M.; Lam, Karen S.L.

doi:10.1016/j.bbrc.2012.06.017

Cited by 54 publications

(41 citation statements)

References 43 publications

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“…Sandwich enzyme-linked immunosorbent assay (ELISA) was performed as described previously [58] by mouse Beta Amyloid 42 and human Beta Amyloid 42 ELISA kits (Thermo Fisher Scientific, US).…”

Section: Methodsmentioning

confidence: 99%

“…Brown color staining was developed and counterstained with hematoxylin. Quantification of staining was performed as described previously [58, 61]. For immunofluorescent staining, sections were incubated with rabbit anti-AdipoR1 (ab70362, Abcam, UK) at 4 °C overnight, followed by Donkey anti-rabbit IgG Alexa Fluor® 594-conjugated secondary antibody (Thermofisher, US) for 30 mins.…”

Section: Methodsmentioning

confidence: 99%

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Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Cheng

Jian

et al. 2016

Mol Neurodegeneration

134

137

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BackgroundInsulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer’s disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer’s-like pathology in mice.MethodsTo study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment.ResultsAged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ42 level, Aβ deposition, hyperphosphorylated Tau proteins, microgliosis and astrogliosis with increased cerebral IL-1β and TNFα levels that associated with increased neuronal apoptosis and reduced synaptic proteins levels, suggesting APN deficiency may lead to neuronal and synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed attenuated AMPK phosphorylation and impaired insulin signaling including decreased Akt induction and increased GSK3β activation in the hippocampus and frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with reduced pAkt induction upon intracerebral insulin injection. Consistently, APN treatment in SH-SY5Y cells with insulin resistance and overexpressing Aβ induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the induction was blocked by compound C, indicating APN can enhance neuronal insulin sensitivity through AMPK activation.ConclusionOur results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0136-x) contains supplementary material, which is available to authorized users.

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“…Sandwich enzyme-linked immunosorbent assay (ELISA) was performed as described previously [58] by mouse Beta Amyloid 42 and human Beta Amyloid 42 ELISA kits (Thermo Fisher Scientific, US).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Cheng

Jian

et al. 2016

Mol Neurodegeneration

134

137

View full text Add to dashboard Cite

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“…Cells were plated onto poly-D-lysine-coated 24-well chamber slides at 1.0 × 10 5 cells/well for immunofluorescence staining analysis, and plated in 96-well plates at 9.0 × 10 3 cells/well for MTT analysis. There were six groups in our experiments: control group and groups I to V. The control group, group I, and group II were successively treated with equivalent volumes of FBS-free DMEM, 100 nM Aβ 1–42 oligomers and 1 μM Aβ 1–42 oligomers for 24 h (Ferreira et al 2012; Ito et al 2012; Zhou et al 2012); groups III, IV, and V were treated with 100 nM human recombinant insulin (Novo Nordisk, Bagsvard, Denmark) for 30 min after the treatments with DMEM vehicle, 100 nM Aβ 1–42 oligomers and 1 μM Aβ 1–42 oligomers, respectively (Bomfim et al 2012; De Felice et al 2009; Ji et al 2011). …”

Section: Methodsmentioning

confidence: 99%

Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes

Han

Yang

et al. 2015

Cell Mol Neurobiol

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The excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), mostly located on astrocytes, are the main mediators for glutamate clearance in humans. Malfunctions of these transporters may lead to excessive glutamate accumulation and subsequent excitotoxicity to neurons, which has been implicated in many kinds of neurodegenerative disorders including Alzheimer’s disease (AD). Yet, the specific mechanism of the glutamate system dysregulation remains vague. To explore whether the insulin/protein kinase B (Akt)/EAAT signaling in human astrocytes could be disturbed by beta-amyloid protein (Aβ) and be protected by insulin, we incubated HA-1800 cells with varying concentrations of Aβ1–42 oligomers and insulin. Then the alterations of several key substrates in this signal transduction pathway were determined. Our results showed that expressions of insulin receptor, phospho-insulin receptor, phospho-protein kinase B, phospho-mammalian target of rapamycin, and EAAT1 and EAAT2 were decreased by the Aβ1–42 oligomers in a dose-dependent manner (p < 0.05) and this trend could be recovered by insulin treatment (p < 0.05). However, the expressions of total Akt and mTOR were invariant (p > 0.05), and the mRNA levels of EAAT1 and EAAT2 were also unchanged (p > 0.05). Taken together, this study indicates that Aβ1–42 oligomers could cause disturbances in insulin/Akt/EAAT signaling in astrocytes, which might be responsible for AD onset and progression. Additionally, insulin can exert protective functions to the brain by modulating protein modifications or expressions.

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“…Automatic handling and detection system might be enhanced the accuracy of the diagnostic results. Considering the concentration of Aβ in an AD patient′s plasma is more or less than tens of pg/mL (Zhou et al, 2012), we guess that this platform might detect Aβ in a blood sample with high sensitivity if the pretreatment protocol of the blood sample were well established.…”

Section: Detection Of Aβ With Mds Assay In the Microfluidic Chipmentioning

confidence: 99%

Magnetic bead droplet immunoassay of oligomer amyloid β for the diagnosis of Alzheimer′s disease using micro-pillars to enhance the stability of the oil–water interface

Kim

Kang

et al. 2015

Biosensors and Bioelectronics

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Plasma amyloid-β oligomers level is a biomarker for Alzheimer’s disease diagnosis

Cited by 54 publications

References 43 publications

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes

Magnetic bead droplet immunoassay of oligomer amyloid β for the diagnosis of Alzheimer′s disease using micro-pillars to enhance the stability of the oil–water interface

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