Human platelets release amyloid peptides β1-40 and β1-42 in response to haemostatic, immune, and hypoxic stimuli
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Human platelets release amyloid peptides β1-40 and β1-42 in response to haemostatic, immune, and hypoxic stimuli. / Wolska, Nina; Celikag, Meral; Failla, Antonio Virgilio; Tarafdar, Anuradha; Renné, Thomas; Torti, Mauro; Canobbio, Ilaria; Pula, Giordano.
In: RES PRACT THROMB HAE, Vol. 7, No. 4, 100154, 05.2023.Research output: SCORING: Contribution to journal › Short publication › Research › peer-review
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T1 - Human platelets release amyloid peptides β1-40 and β1-42 in response to haemostatic, immune, and hypoxic stimuli
AU - Wolska, Nina
AU - Celikag, Meral
AU - Failla, Antonio Virgilio
AU - Tarafdar, Anuradha
AU - Renné, Thomas
AU - Torti, Mauro
AU - Canobbio, Ilaria
AU - Pula, Giordano
N1 - Brief Report
PY - 2023/5
Y1 - 2023/5
N2 - BACKGROUND: Platelets contain high levels of amyloid β (Aβ) peptides and have been suggested to participate in the deposition of amyloid plaques in Alzheimer's Disease (AD).OBJECTIVES: This study aimed to determine whether human platelets release pathogenic Aβ peptides Aβ1-42 and Aβ1-40 and to characterise the mechanisms regulating this phenomenon.METHODS AND RESULTS: Enzyme-linked immunosorbent assays (ELISAs) revealed that the haemostatic stimulus thrombin and the pro-inflammatory molecule lipopolysaccharide (LPS) induce platelet release of both Aβ1-42 and Aβ1-40. Notably, LPS preferentially induced the release of Aβ1-42, which was potentiated by the reduction of oxygen from atmospheric levels to physiological hypoxia. The selective β secretase (BACE) inhibitor LY2886721 showed no effect on the release of either Aβ1-40 or Aβ1-42 in our ELISA experiments. This suggested a store-and-release mechanism that was confirmed in immunostaining experiments showing co-localisation of cleaved Aβ peptides with platelet alpha granules.CONCLUSIONS: Taken together, our data suggest that human platelets release pathogenic Aβ peptides as a result of a store-and-release mechanism rather than a de novo proteolytic event. Although further studies are required to fully characterise this phenomenon, we suggest the possibility of a role for platelets in the deposition of Aβ peptides and the formation of amyloid plaques. Interestingly, the combination of hypoxia and inflammation that we simulated in vitro with reduced oxygen tension and LPS may increase the release of fibrillogenic Aβ1-42 and, consequently, exacerbate amyloid plaque deposition in the brain of AD patients.
AB - BACKGROUND: Platelets contain high levels of amyloid β (Aβ) peptides and have been suggested to participate in the deposition of amyloid plaques in Alzheimer's Disease (AD).OBJECTIVES: This study aimed to determine whether human platelets release pathogenic Aβ peptides Aβ1-42 and Aβ1-40 and to characterise the mechanisms regulating this phenomenon.METHODS AND RESULTS: Enzyme-linked immunosorbent assays (ELISAs) revealed that the haemostatic stimulus thrombin and the pro-inflammatory molecule lipopolysaccharide (LPS) induce platelet release of both Aβ1-42 and Aβ1-40. Notably, LPS preferentially induced the release of Aβ1-42, which was potentiated by the reduction of oxygen from atmospheric levels to physiological hypoxia. The selective β secretase (BACE) inhibitor LY2886721 showed no effect on the release of either Aβ1-40 or Aβ1-42 in our ELISA experiments. This suggested a store-and-release mechanism that was confirmed in immunostaining experiments showing co-localisation of cleaved Aβ peptides with platelet alpha granules.CONCLUSIONS: Taken together, our data suggest that human platelets release pathogenic Aβ peptides as a result of a store-and-release mechanism rather than a de novo proteolytic event. Although further studies are required to fully characterise this phenomenon, we suggest the possibility of a role for platelets in the deposition of Aβ peptides and the formation of amyloid plaques. Interestingly, the combination of hypoxia and inflammation that we simulated in vitro with reduced oxygen tension and LPS may increase the release of fibrillogenic Aβ1-42 and, consequently, exacerbate amyloid plaque deposition in the brain of AD patients.
U2 - 10.1016/j.rpth.2023.100154
DO - 10.1016/j.rpth.2023.100154
M3 - Short publication
C2 - 37222974
VL - 7
JO - RES PRACT THROMB HAE
JF - RES PRACT THROMB HAE
SN - 2475-0379
IS - 4
M1 - 100154
ER -