Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer’s Disease versus Age-Matched Controls: A Presymptomatic Stage Study

Recent mouse studies of the presymptomatic stage of Alzheimer’s disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFαcontributes to increased Aβproduction from the Aβprecursor protein (APP), we assessed a putative correlation between APP/Aβand TNFαduring the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβwas not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFαand APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD.

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Characterization of Serum Exosomes from a Transgenic Mouse Model of Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205016666190321155422 ◽

2019 ◽

Vol 16 (5) ◽

pp. 388-395 ◽

Cited By ~ 4

Author(s):

Hector Rosas-Hernandez ◽

Elvis Cuevas ◽

James B. Raymick ◽

Bonnie L. Robinson ◽

Syed F. Ali ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Amyloid Angiopathy ◽

Western Blots ◽

Model Of Alzheimer’S Disease ◽

Serum Exosomes

Background: Alzheimer’s Disease (AD) is the most common type of dementia characterized by amyloid plaques containing Amyloid Beta (Aβ) peptides and neurofibrillary tangles containing tau protein. In addition to neuronal loss, Cerebral Amyloid Angiopathy (CAA) commonly occurs in AD. CAA is characterized by Aβ deposition in brain microvessels. Recent studies have suggested that exosomes (cell-derived vesicles containing a diverse cargo) may be involved in the pathogenesis of AD. Objective: Isolate and characterize brain-derived exosomes from a transgenic mouse model of AD that presents CAA. Methods: Exosomes were isolated from serum obtained from 13-month-old wild type and AD transgenic female mice using an exosome precipitation solution. Characterization of exosomal proteins was performed by western blots and dot blots. Results: Serum exosomes were increased in transgenic mice compared to wild types as determined by increased levels of the exosome markers flotillin and alix. High levels of neuronal markers were found in exosomes, without any difference any between the 2 groups. Markers for endothelial-derived exosomes were decreased in the transgenic model, while astrocytic-derived exosomes were increased. Exosome characterization showed increased levels of oligomeric Aβ and oligomeric and monomeric forms tau on the transgenic animals. Levels of amyloid precursor protein were also increased. In addition, pathological and phosphorylated forms of tau were detected, but no difference was observed between the groups. Conclusion: These data suggest that monomeric and oligomeric forms of Aβ and tau are secreted into serum via brain exosomes, most likely derived from astrocytes in the transgenic mouse model of AD with CAA. Studies on the implication of this event in the propagation of AD are underway.

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