Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors

Lilia Y Kucheryavykh, Jescelica Ortiz-Rivera, Yuriy V Kucheryavykh, Astrid Zayas-Santiago, Amanda Diaz-Garcia, Mikhail Y Inyushin, Lilia Y Kucheryavykh, Jescelica Ortiz-Rivera, Yuriy V Kucheryavykh, Astrid Zayas-Santiago, Amanda Diaz-Garcia, Mikhail Y Inyushin

Abstract

Immunostaining with specific antibodies has shown that innate amyloid beta (Aβ) is accumulated naturally in glioma tumors and nearby blood vessels in a mouse model of glioma. In immunofluorescence images, Aβ peptide coincides with glioma cells, and enzyme-linked immunosorbent assay (ELISA) have shown that Aβ peptide is enriched in the membrane protein fraction of tumor cells. ELISAs have also confirmed that the Aβ(1-40) peptide is enriched in glioma tumor areas relative to healthy brain areas. Thioflavin staining revealed that at least some amyloid is present in glioma tumors in aggregated forms. We may suggest that the presence of aggregated amyloid in glioma tumors together with the presence of Aβ immunofluorescence coinciding with glioma cells and the nearby vasculature imply that the source of Aβ peptides in glioma can be systemic Aβ from blood vessels, but this question remains unresolved and needs additional studies.

Keywords: Aβ peptide; amyloid; glioma; platelets.

Conflict of interest statement

The authors declare that they have no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Aβ peptide immunoreactivity (green) in glioma cells and in nearby blood vessels. (A) A small glioma tumor near a broken blood vessel. Aβ peptide immunoreactivity (green) visible in glioma cells (white arrow) and in blood vessels. Erythrocytes released from the broken vessel are also marked with Aβ-related immunofluorescence (yellow arrow). (B) A larger glioma tumor in which a broken blood vessel passes through the tumor (more clearly visible in the 3D image of this tumor shown in Figure S1B), and white arrows indicate glioma cells marked by green immunofluorescence representing Aβ peptide. For A and B, astrocytes are indicated by immunoreactivity to GFAP (red) and cell nuclei by DAPI staining (blue). Scale bar, 20 µm. (See also supplemental confocal 3D images of the same tumors in Figure S1A,B, respectively).
Figure 2
Figure 2
(A) The relative amount of Aβ40 in the glioma tissue is elevated. (B) Aβ40 in glioma tumor tissue is concentrated in the cell membrane fraction.
Figure 3
Figure 3
Aggregated amyloid visualized by staining with thioflavin T (green) and thioflavin S (red) inside the glioma tumor body. The white arrow shows the glioma tumor body visible in the brain slice.

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