Platelets Are Responsible for the Accumulation of β-amyloid in Blood Clots Inside and Around Blood Vessels in Mouse Brain After Thrombosis

Brain Res Bull. 2017 Jan;128:98-105. doi: 10.1016/j.brainresbull.2016.11.008. Epub 2016 Nov 28.

Abstract

Introduction: Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated.

Methods: We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains.

Results: Both in vivo results and electron microscopy revealed that platelets were 300-500 times more concentrated in clots than in non-clotted blood. After thrombosis in control mice, but not in thrombocytopenic animals, Aβ immunofluorescence was present inside blood vessels in the visual cortex and around capillaries in the entorhinal cortex.

Conclusion: The increased concentration of platelets allows enhanced release of Aβ during thrombosis, suggesting an additional source of Aβ in the brains of Alzheimer's patients that may arise if frequent micro-thrombosis events occur in their brains.

Keywords: Alzheimer; Aβ-peptide; Platelets; Thrombosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Cerebrovascular Disorders / metabolism*
  • Cerebrovascular Disorders / pathology
  • Disease Models, Animal
  • Entorhinal Cortex / blood supply
  • Entorhinal Cortex / metabolism*
  • Entorhinal Cortex / pathology
  • Female
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microscopy, Electron
  • Photic Stimulation
  • Platelet Count
  • Thrombocytopenia / metabolism
  • Thrombocytopenia / pathology
  • Thrombosis / metabolism*
  • Thrombosis / pathology
  • Visual Cortex / blood supply
  • Visual Cortex / metabolism*
  • Visual Cortex / pathology

Substances

  • Amyloid beta-Peptides