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. 2017 Apr 4:7:45496.
doi: 10.1038/srep45496.

Cortical laminar tau deposits and activated astrocytes in Alzheimer's disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography

Laetitia Lemoine  1 , Laure Saint-Aubert  1 , Inger Nennesmo  2 , Per-Göran Gillberg  1 , Agneta Nordberg  1   3
Affiliations

Cortical laminar tau deposits and activated astrocytes in Alzheimer's disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography

Laetitia Lemoine et al. Sci Rep. .

Abstract

Hyperphosphorylated tau protein deposits and, inflammatory processes are characteristic components of Alzheimer disease (AD) pathology. We here aimed to visualize in vitro the distribution of tau deposits and activated astrocytes across the cortical layers in autopsy AD brain tissue using the radiotracers 3H-THK5117 and 3H-deprenyl. 3H-THK5117 and 3H-deprenyl autoradiographies were carried out on frozen brain sections from three AD patients and one healthy control. 3H-THK5117 showed a distinct laminar cortical binding similar to 3H-deprenyl autoradiography, with an extensive binding in the superficial and deep layers of the temporal neocortices, whereas the middle frontal gyrus showed an even binding throughout the layers. Globally, eventhough some differences could be observed, AT8 (tau) and GFAP (astrocyte) immunostaining showed a laminar pattern comparable to their corresponding radiotracers within each AD case. Some variability was observed between the AD cases reflecting differences in disease phenotype. The similar laminar cortical brain distribution of tau deposits and activated astrocytes supports the hypothesis of a close pathological interconnection. The difference in regional binding patterns of 3H-THK5117 and AT8 antibody staining suggest additional tau binding sites detectable by 3H-THK5117.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Study layout illustrated in AD case 1.
Autoradiography with 3H-THK5117 (A), 3H-deprenyl (B) and 3H-PiB (C) on frozen large hemisphere samples from AD case 1. Immunostaining on paraffin sections from the corresponding contralateral hemisphere in the entorhinal gyrus with AT8 (D), GFAP (E) and Clone 6F/3D (F). A zooming on the different layers is presented in D’, E’ and F’ for AT8, GFAP and clone 6F/3D, respectively.
Figure 2
Figure 2. Correspondence between 3H-THK5117 autoradiography and AT8 staining.
Autoradiography on frozen sections from AD brains 1, 2 and 3 using 3H-THK5117 are respectively shown for the temporal cortex in (A,E,I) and for the frontal cortex in (C,G,K). Corresponding AT8 immunostaining on paraffin section from the contralateral hemisphere is presented in (B,F,J and D,H,L) for temporal and frontal cortex, respectively.
Figure 3
Figure 3. Laminar binding profiles of 3H-THK5117 and 3H-Deprenyl from selections within the entorhinal cortex (BA28) and parahippocampal gyrus (BA36).
The 3H-THK5117 binding profiles are presented in (A,B,C,D) (A) AD case 1, (B) control case, (C) AD case 2, and (D) AD case 3. 3H-Deprenyl binding profiles are presented in (E,F,G,H) (E) AD case 1, (F) control case, (G) AD case 2 and (H) AD case 3. The different colors correspond to different selection in the region of interest.
Figure 4
Figure 4. Laminar binding profiles from selections within the fusiform gyrus (BA37).
3H-THK5117 binding profiles are presented in (A,B,C,D) (A) AD case 1; (B) AD case 2; (C) AD case 3 and (D) control case 4. 3H-Deprenyl binding profiles are presented in (E,F,G,H) (E) AD case 1; (F) AD case 2; (G) AD case 3 and (H) control case. The different colors correspond to different selection in the region of interest.
Figure 5
Figure 5. Laminar binding profiles from selections within the inferior temporal gyrus (BA20).
3H-THK5117 binding profiles are presented in (A,B,C,D) (A) AD case 1; (B) AD case 2; (C) AD case 3 and (D) control case. 3H-Deprenyl binding profiles are presented in (E,F,G,H) (E) AD case 1; (F) AD case 2; (G) AD case 3 and (H) control case. The different colors correspond to different selection in the region of interest.
Figure 6
Figure 6. Laminar binding profiles from selections within the middle frontal gyrus (BA06).
3H-THK5117 binding profiles are presented in (A,B,C,D) (A) AD case 1; (B) AD case 2; (C) AD case 3 and (D) control case. 3H-Deprenyl binding profiles are presented in (E,F,G,H) (E) AD case 1; (F) AD case 2; (G) AD case 3 and (H) control case. The different colors correspond to different selection in the region of interest.
Figure 7
Figure 7. Correspondence between AT8 and GFAP staining in paraffin sections.
Immunostaining in each regions of interest is shown for the three AD cases. For AD Case 1, AT8: A–D and GFAP: A’–D’. For AD Case 2, AT8: E–H and GFAP: E’–H’. For AD Case 3, AT8: I–K and GFAP: I’–K’. Note that staining in the inferior temporal was not available for case 3. ×40 zoomed, scale bar = 100 µm.
See this image and copyright information in PMC

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