Amyloid β-interacting partners in Alzheimer's disease: From accomplices to possible therapeutic targets

Han, Sun Ho; Park, Jong Chan; Mook‐Jung, Inhee

doi:10.1016/j.pneurobio.2015.12.004

Cited by 60 publications

(43 citation statements)

References 343 publications

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“…Aβ peptide was purchased from Bachem Americas, Inc. (Torrance, CA, USA) and prepared as described previously [41]. HSA (Sigma-Aldrich) was used for mimicking the plasma sample condition because it is the most abundant protein in the human plasma [25, 42, 43]. …”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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BackgroundPlasma β-amyloid (Aβ) is a potential candidate for an Alzheimer’s disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis.MethodsWe predicted the brain amyloid deposit by measuring the plasma Aβ levels. This cross-sectional study included 353 participants (215 cognitively normal, 79 with mild cognitive impairment, and 59 with AD dementia) who underwent Pittsburgh-compound B positron emission tomography (PiB-PET) scans. We treated a mixture of protease inhibitors and phosphatase inhibitors (MPP) and detected plasma Aβ42 and Aβ40 (MPP-Aβ42 and MPP-Aβ40) in a stable manner using xMAP technology.ResultsMPP-Aβ40 and MPP-Aβ42/40 (MPP-Aβs) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB–) (P < 0.0001). Furthermore, MPP-Aβ40 (P < 0.0001, r = 0.23) and MPP-Aβ42/40 ratio (P < 0.0001, r = –0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-Aβ42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition.ConclusionsMPP-Aβ might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0248-8) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…These inflammatory microglia and astrocytes, often found in the vicinity of plaques and tangles, continue to produce more cytokines and other inflammatory molecules. Perhaps particularly pernicious in this regard is the capacity of Aβ itself to directly activate TLR4 and receptor for advanced glycation end-products (RAGE) to further activate microglia and promote inflammation [43]. …”

Section: Cns Diseases Involving Psychological Stress Inflammation Anmentioning

confidence: 99%

Stressed and Inflamed, Can GSK3 Be Blamed?

Jope

Cheng

Lowell

et al. 2017

Trends in Biochemical Sciences

101

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Psychological stress has a pervasive influence on our lives. In many cases adapting to stress strengthens organisms, but chronic or severe stress is usually harmful. One surprising outcome of psychological stress is activation of an inflammatory response, resembling inflammation caused by infection or trauma. Excessive psychological stress and the consequential inflammation in the brain can increase susceptibility to psychiatric diseases, such as depression, and impair learning and memory, including in some patients with cognitive deficits. An emerging target to control detrimental outcomes of stress and inflammation is glycogen synthase kinase-3 (GSK3). GSK3 promotes inflammation, partly by regulating key transcription factors in the inflammation signaling pathway, and GSK3 can impair learning by promoting inflammation and by inhibiting long term potentiation (LTP). Drugs inhibiting GSK3 may prove beneficial for controlling mood and cognitive impairments caused by excessive stress and the associated neuroinflammation.

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“…Although overexpression of ApoE receptors are expected to increase ApoE-amyloid β clearance and decrease amyloid β level, transgenic mouse model studies provided unexpected findings. Overexpression of LRP minireceptor increased toxic amyloid β levels and caused the deficits in learning and memory, whereas LDLR overexpression decreased amyloid β accumulation [18]. To regulate the expression of endogenous LDLR, one study investigated whether an inactivation of LDLR degradation pathway will increase the clearance of ApoE and amyloid β [19].…”

Section: Regulation Of Apolipoprotein E Lipidation and Metabolismmentioning

confidence: 99%

Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease

Liao

Yoon

Kim

2017

Current Opinion in Lipidology

130

100

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Purpose of reviewAPOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease.Recent findingsApoE isoforms have differential effects on amyloid β metabolism. Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment. Activation of liver X receptor and retinoid X receptor pathway induces ABCA1 and other genes, leading to amyloid β clearance. Inhibition of the negative regulators of ABCA1, such as microRNA-33, also induces ABCA1 and decreases the levels of ApoE and amyloid β. In addition, genetic inactivation of an E3 ubiquitin ligase, myosin regulatory light chain interacting protein, increases LDL receptor levels and inhibits amyloid accumulation. Although amyloid β-dependent pathways have been extensively investigated, there have been several recent studies linking ApoE with vascular function, neuroinflammation, metabolism, synaptic plasticity, and transcriptional regulation. For example, ApoE was identified as a ligand for a microglial receptor, TREM2, and studies suggested that ApoE may affect the TREM2-mediated microglial phagocytosis.SummaryEmerging data suggest that ApoE affects several amyloid β-independent pathways. These underexplored pathways may provide new insights into Alzheimer's disease pathogenesis. However, it will be important to determine to what extent each mechanism contributes to the pathogenesis of Alzheimer's disease.

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Amyloid β-interacting partners in Alzheimer's disease: From accomplices to possible therapeutic targets

Cited by 60 publications

References 343 publications

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

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

Stressed and Inflamed, Can GSK3 Be Blamed?

Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease

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