Impact of Amyloid-β on Platelet Mitochondrial Function and Platelet-Mediated Amyloid Aggregation in Alzheimer's Disease.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is characterized by an accumulation of amyloid β (Aβ) peptides in the brain and mitochondrial dysfunction. Platelet activation is enhanced in AD and platelets contribute to AD pathology by their ability to facilitate soluble Aβ to form Aβ aggregates. Thus, anti-platelet therapy reduces the formation of cerebral amyloid angiopathy in AD transgenic mice. Platelet mitochondrial dysfunction plays a regulatory role in thrombotic response, but its significance in AD is unknown and explored herein.

METHODS:

The effects of Aβ-mediated mitochondrial dysfunction in platelets were investigated in vitro.

RESULTS:

Aβ40 stimulation of human platelets led to elevated reactive oxygen species (ROS) and superoxide production, while reduced mitochondrial membrane potential and oxygen consumption rate. Enhanced mitochondrial dysfunction triggered platelet-mediated Aβ40 aggregate formation through GPVI-mediated ROS production, leading to enhanced integrin αIIbβ3 activation during synergistic stimulation from ADP and Aβ40. Aβ40 aggregate formation of human and murine (APP23) platelets were comparable to controls and could be reduced by the antioxidant vitamin C.

CONCLUSIONS:

Mitochondrial dysfunction contributes to platelet-mediated Aβ aggregate formation and might be a promising target to limit platelet activation exaggerated pathological manifestations in AD.

• Authors: Lili Donner, Tobias Feige, Carolin Freiburg, Laura Mara Toska, Andreas S Reichert, Madhumita Chatterjee, Margitta Elvers
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 17 (Sep 06 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34502546 (Publication Type: Journal Article)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• Integrins
• Mitochondrial Proteins
• Reactive Oxygen Species

Topics

• Alzheimer Disease (genetics, metabolism)
• Amyloid (metabolism)
• Amyloid beta-Peptides (metabolism, pharmacology)
• Animals
• Blood Platelets (cytology, drug effects, metabolism)
• Cells, Cultured
• Humans
• Integrins (metabolism)
• Membrane Potential, Mitochondrial (genetics)
• Mice, Inbred C57BL
• Mice, Transgenic
• Mitochondria (drug effects, metabolism)
• Mitochondrial Proteins (metabolism)
• Oxygen Consumption (drug effects)
• Platelet Activation (drug effects)
• Platelet Function Tests (methods)
• Protein Aggregation, Pathological (metabolism)
• Reactive Oxygen Species (metabolism)