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Platelets in the Alzheimer's disease brain: do they play a role in cerebral amyloid angiopathy?

Kniewallner KM, Ehrlich D, Kiefer A, Marksteiner J, Humpel C - Curr Neurovasc Res (2015)

Bottom Line: The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis.In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels.Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.

View Article: PubMed Central - PubMed

Affiliation: Deparment of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck, Austria. christian.humpel@i-med.ac.at.

ABSTRACT
Alzheimer's disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular injury. The aim of the present study was to explore the presence and migration of platelets (thrombocytes) to sites of small vascular bleedings and/or to beta-amyloid plaques in the brain. We infused fluorescently labeled red PKH26 mouse platelets into transgenic Alzheimer mice overexpressing APP with Swedish/Dutch/Iowa mutations (APP_SDI) and explored if platelets migrate into the brain. Further we studied whether platelets accumulate in the vicinity of β-amyloid plaques. Our animal data shows that infused platelets are found in the liver and partly in the lung, while in the brain platelets were visible to a minor degree. In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels. In the brain of Alzheimer postmortem patients platelets could be detected by immunohistochemistry for CD41 and CD62P, but the majority was found in vessels with or without beta-amyloid load, and only a few single platelets migrated deeper into the brain. Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.

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Platelets in a human postmortem Alzheimer brain. Paraffin embedded brain sections were stained for beta-amyloid (Alexa 350, blue,EX 260/40; EM 470/40, ADGJ) and CD62P (Alexa 488, green, EX 480/40 nm, EM 527/30 nm, BEHK) by fluorescenceimmunohistochemistry. Fig. CFIL show the merged pictures. Example 1 (ABC) shows platelets (arrows) not associated with a beta-amyloidplaque (*). Example 2 (DEF) shows platelets (arrows) associated directly with a plaque (*) or in a vessel close to a plaque. Example 3 (GHI)shows platelets (arrow) in a beta-amyloid (*) vessel (c) representing cerebral amyloid angiopathy. Example 4 (JKL) shows platelets (arrow)in a vessel wall adjacent to the brain tissue probly entering the brain. Scale bar = 35 µm. (The color version of the figure is available in theelectronic copy of the article).
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Figure 5: Platelets in a human postmortem Alzheimer brain. Paraffin embedded brain sections were stained for beta-amyloid (Alexa 350, blue,EX 260/40; EM 470/40, ADGJ) and CD62P (Alexa 488, green, EX 480/40 nm, EM 527/30 nm, BEHK) by fluorescenceimmunohistochemistry. Fig. CFIL show the merged pictures. Example 1 (ABC) shows platelets (arrows) not associated with a beta-amyloidplaque (*). Example 2 (DEF) shows platelets (arrows) associated directly with a plaque (*) or in a vessel close to a plaque. Example 3 (GHI)shows platelets (arrow) in a beta-amyloid (*) vessel (c) representing cerebral amyloid angiopathy. Example 4 (JKL) shows platelets (arrow)in a vessel wall adjacent to the brain tissue probly entering the brain. Scale bar = 35 µm. (The color version of the figure is available in theelectronic copy of the article).

Mentions: In order to investigate the presence of platelets in the human brain, 2 controls and 3 Alzheimer brains (Table 1) were stained for platelet marker CD41 and CD62P. Again visualization under the green fluorescence filter (EX 480/40 nm, EM 527/30 nm) compared to the red fluorescence filter (EX 535/50, EM 610/75) showed the specificity of the staining and not only autofluorescence (Fig. 4). In control brains only very few CD41+ or CD62P+ platelets were found outside of vessels in the brain tissue, while the majority was seen within vessels (Fig. 4). In Alzheimer brains, the characteristic neuropathological features were found with intensely stained βA plaques and ßA depositions in vessels (CAA) (Fig. 5) Only very few CD62P+ platelets were seen in the tissue not associated with bA plaques (Fig.; Fig. 6). Many CD62P+ platelets were associated directly with a bA plaque or with a vessel close to a bA plaque (Fig. 5; Fig. 6). The majority of CD62P+ platelets was seen in vessels without bA plaques or associated with cerebral amyloid angiopathy (Fig. 6). The platelets in asscociation with ßA plaques also displayed a discoid shape and were not different from platelets found in the vessels.


Platelets in the Alzheimer's disease brain: do they play a role in cerebral amyloid angiopathy?

Kniewallner KM, Ehrlich D, Kiefer A, Marksteiner J, Humpel C - Curr Neurovasc Res (2015)

Platelets in a human postmortem Alzheimer brain. Paraffin embedded brain sections were stained for beta-amyloid (Alexa 350, blue,EX 260/40; EM 470/40, ADGJ) and CD62P (Alexa 488, green, EX 480/40 nm, EM 527/30 nm, BEHK) by fluorescenceimmunohistochemistry. Fig. CFIL show the merged pictures. Example 1 (ABC) shows platelets (arrows) not associated with a beta-amyloidplaque (*). Example 2 (DEF) shows platelets (arrows) associated directly with a plaque (*) or in a vessel close to a plaque. Example 3 (GHI)shows platelets (arrow) in a beta-amyloid (*) vessel (c) representing cerebral amyloid angiopathy. Example 4 (JKL) shows platelets (arrow)in a vessel wall adjacent to the brain tissue probly entering the brain. Scale bar = 35 µm. (The color version of the figure is available in theelectronic copy of the article).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4442621&req=5

Figure 5: Platelets in a human postmortem Alzheimer brain. Paraffin embedded brain sections were stained for beta-amyloid (Alexa 350, blue,EX 260/40; EM 470/40, ADGJ) and CD62P (Alexa 488, green, EX 480/40 nm, EM 527/30 nm, BEHK) by fluorescenceimmunohistochemistry. Fig. CFIL show the merged pictures. Example 1 (ABC) shows platelets (arrows) not associated with a beta-amyloidplaque (*). Example 2 (DEF) shows platelets (arrows) associated directly with a plaque (*) or in a vessel close to a plaque. Example 3 (GHI)shows platelets (arrow) in a beta-amyloid (*) vessel (c) representing cerebral amyloid angiopathy. Example 4 (JKL) shows platelets (arrow)in a vessel wall adjacent to the brain tissue probly entering the brain. Scale bar = 35 µm. (The color version of the figure is available in theelectronic copy of the article).
Mentions: In order to investigate the presence of platelets in the human brain, 2 controls and 3 Alzheimer brains (Table 1) were stained for platelet marker CD41 and CD62P. Again visualization under the green fluorescence filter (EX 480/40 nm, EM 527/30 nm) compared to the red fluorescence filter (EX 535/50, EM 610/75) showed the specificity of the staining and not only autofluorescence (Fig. 4). In control brains only very few CD41+ or CD62P+ platelets were found outside of vessels in the brain tissue, while the majority was seen within vessels (Fig. 4). In Alzheimer brains, the characteristic neuropathological features were found with intensely stained βA plaques and ßA depositions in vessels (CAA) (Fig. 5) Only very few CD62P+ platelets were seen in the tissue not associated with bA plaques (Fig.; Fig. 6). Many CD62P+ platelets were associated directly with a bA plaque or with a vessel close to a bA plaque (Fig. 5; Fig. 6). The majority of CD62P+ platelets was seen in vessels without bA plaques or associated with cerebral amyloid angiopathy (Fig. 6). The platelets in asscociation with ßA plaques also displayed a discoid shape and were not different from platelets found in the vessels.

Bottom Line: The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis.In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels.Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.

View Article: PubMed Central - PubMed

Affiliation: Deparment of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck, Austria. christian.humpel@i-med.ac.at.

ABSTRACT
Alzheimer's disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular injury. The aim of the present study was to explore the presence and migration of platelets (thrombocytes) to sites of small vascular bleedings and/or to beta-amyloid plaques in the brain. We infused fluorescently labeled red PKH26 mouse platelets into transgenic Alzheimer mice overexpressing APP with Swedish/Dutch/Iowa mutations (APP_SDI) and explored if platelets migrate into the brain. Further we studied whether platelets accumulate in the vicinity of β-amyloid plaques. Our animal data shows that infused platelets are found in the liver and partly in the lung, while in the brain platelets were visible to a minor degree. In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels. In the brain of Alzheimer postmortem patients platelets could be detected by immunohistochemistry for CD41 and CD62P, but the majority was found in vessels with or without beta-amyloid load, and only a few single platelets migrated deeper into the brain. Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.

Show MeSH
Related in: MedlinePlus