S100A9 Knockout Decreases the Memory Impairment and Neuropathology in Crossbreed Mice of Tg2576 and S100A9 Knockout Mice Model

Kim, Hee Jin; Chang, Keun A.; Ha, Tae Young; Kim, Jeong‐A; Ha, Sungji; Shin, Ki Young; Moon, Cheil; Nacken, Wolfgang; Kim, Hye Sun; Suh, Yoo‐Hun

doi:10.1371/journal.pone.0088924

Cited by 38 publications

(31 citation statements)

References 60 publications

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“…To address the possibility that mild blast exposure may alter perivascular phospho-tau expression in blast exposed mice we performed confocal microscopy using a well-characterized mouse phospho-tau monoclonal antibody (pS396) (Hoffmann et al, 1997, Bennett et al, 2013, Kim et al, 2014). We found aberrant phospho-tau accumulation in perivascular regions of non-penetrating small (~8–15 μm diameter) cortical microvessels in 100% (n=5/5) of BOP-exposed mice and none (n=0/5) of the sham treated mice at 1 hour post-exposure (Figure 6A).…”

Section: Resultsmentioning

confidence: 99%

Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction

et al. 2016

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Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased amoeboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3X) blast exposure. Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses.

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Section: Resultsmentioning

confidence: 99%

Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction

et al. 2016

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“…Among the 5 classifier proteins, S100A9 is the only one associated with AD [67][68][69][70][71][72]. S100A9 in the brain was reported to associate with the neuropathological hallmarks of AD and contribute to AD pathology [67][68][69][70][71][72].…”

Section: Discussionmentioning

confidence: 99%

“…S100A9 in the brain was reported to associate with the neuropathological hallmarks of AD and contribute to AD pathology [67][68][69][70][71][72]. For example, induction of S100A9 was observed in the brain of AD animal model Tg2576 and in human AD brain.…”

Section: Discussionmentioning

confidence: 99%

A Candidate Plasma Protein Classifier to Identify Alzheimer's Disease

Zhao

Lejnine

Spond

et al. 2014

JAD

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Biomarkers currently used in the aid for the diagnosis of Alzheimer's disease (AD) are cerebrospinal fluid (CSF) protein markers and brain neuroimaging markers. These biomarkers, however, either involve semi-invasive procedures or are costly to measure. Thus, AD biomarkers from more easily accessible body fluids, such as plasma, are very enticing. Using an aptamer-based proteomic technology, we profiled 1,129 plasma proteins of AD patients and non-demented control individuals. A 5-protein classifier for AD identification was constructed in the discovery study with excellent 10-fold cross-validation performance (90.1% sensitivity, 84.2% specificity, 87.9% accuracy, and AUC as 0.94). In an independent validation study, the classifier was applied and correctly predicted AD with 100.0% sensitivity, 80.0% specificity, and 90.0% accuracy, matching or outperforming the CSF Aβ42 and tau biomarkers whose performance were assessed in individual-matched CSF samples obtained at the same visit as plasma sample collection. Moreover, the classifier also correctly predicted mild cognitive impairment, an early pre-dementia state of the disease, with 96.7% sensitivity, 80.0% specificity, and 92.5% accuracy. These studies demonstrate that plasma proteins could be used effectively and accurately to contribute to the clinical diagnosis of AD. Although additional and more diverse cohorts are needed for further validation of the robustness, including the support of postmortem diagnosis, the 5-protein classifier appears to be a promising blood test to contribute diagnosis of AD.

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“…This was also supported by some experiments which showed that knockdown of S100A9 expression ameliorates cognition in AD model mice (Tg2576), and these animals present reduced amyloid plaque formation. In their subsequent study [12], Kim et al developed a novel transgenic animal model of AD by crossbreeding the Tg2576 mouse with the S100A9 knockout (KO) mouse. They notice that S100A9KO/Tg2576 (KO/Tg) mice displayed an increased spatial reference memory in the Morris water maze task and Y-maze task as well as decreased amyloid beta peptide (Aβ) neuropathology because of reduced levels of Aβ, C-terminal fragments of amyloid precursor protein (APP-CT) and phosphorylated TAU and increased expression of anti-inflammatory Interleukins-10 (IL-10) and also decreased expression of inflammatory Interleukins-6 (IL-6) and tumour neurosis factor (TNF)-α when compared with age-matched S100A9WT/Tg2576 (WT/Tg) mice.…”

Section: Introductionmentioning

confidence: 99%

Global dynamics for a model of amyloid fibril formation in pancreatic islet beta cells subjected to a therapy

Massoukou

Noutchie

Mbroh

2020

Journal of Biological Dynamics

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Amyloid polypeptide (IAPP) fibril formation is the main cause of type II diabetes mellitus (T2DM) disease and cardiovascular disease (CVD). Therefore, implementing therapeutic interventions strategies to control IAPP fibril formation plays a crucial role in preventing and managing T2DM disease and CVD. For this purpose, in this paper, we make use of a mathematical model to investigate the effects of drug therapy on the dynamics of amyloid fibril formation (or amyloid plaques). The model is a hybrid system of differential equations consisting of ODEs and (hyperbolic) PDE. The (global) stability analysis is established through the construction of suitable Lyapunov functionals and application of Lasalle's invariance principle. Moreover, stability of the disease steady state is fully determined by a threshold condition, which is based on the total population of IAPP polymers. ARTICLE HISTORY

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S100A9 Knockout Decreases the Memory Impairment and Neuropathology in Crossbreed Mice of Tg2576 and S100A9 Knockout Mice Model

Cited by 38 publications

References 60 publications

Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction

Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction

A Candidate Plasma Protein Classifier to Identify Alzheimer's Disease

Global dynamics for a model of amyloid fibril formation in pancreatic islet beta cells subjected to a therapy

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