β amyloid fragments derived from activated platelets deposit in cerebrovascular endothelium: Usage of a novel blood brain barrier endothelial cell model system

• Published in: Amyloid 2000, Vol.7 (3), p.153-165
• Main Authors: Davies, Theresa A., Long, Heidi J., Eisenhauer, Patricia B., Hastey, Ryan, Cribbs, David H., Fine, Richard E., Simons, Elizabeth R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; amyloid peptide; blood brain barrier; Blood Platelets - metabolism; Blood-Brain Barrier - physiology; Brain - blood supply; Brain - pathology; Cells, Cultured; endothelial cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Fluorescein-5-isothiocyanate - analysis; Fluorescent Dyes - analysis; Humans; Male; Microscopy, Confocal; Middle Aged; Peptide Fragments - metabolism; Platelet Activation; platelets; Protein Processing, Post-Translational; secretases
• ISSN: 1350-6129; 1744-2818
• DOI: 10.3109/13506120009146830

Amyloid precursor protein (AβPP) processing results in generation of amyloid β peptide (Aβ) which deposits in the brain parenchyma and cerebrovasculature of patients with Alzheimer's disease (AD). Evidence that the vascular deposits derive in part from AβPP fragments originating from activated platelets includes findings that individuals who have had multiple small strokes have a higher prevalence of AD compared to individuals who have taken antiplatelet drugs. Thus, determination ofwhether platelet AβPP fragments are capable of traversing the blood-brain barrier (BBB) is critical. We have established that activated platelets from patients with AD retain more surface trans-membrane-bound AβPP (mAβPP) than control platelets. We report here that this mAβPP can be cleaved to Aβ-containing fragments which pass through a novel BBB model system. This model utilizes human BBB endothelial cells (BEC) isolated from brains of patients with AD. These BEC, after exposure to activated platelets which have been surface-labeled with fluorescein and express surface-retained mAβPP, cleave fluorescein-tagged surface proteins, including mAβPP, resulting in passage to the BEC layer. The data confirm that BEC contribute to processing of platelet-derived mAβPP and show that the processing yields Aβ con-tainingfragments which could potentially contribute to cerebrovascular Aβ deposition.