Brain endothelial cell enzymes cleave platelet-retained amyloid precursor protein

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Thrombin-activated platelets in advanced Alzheimer's disease (AD) patients exhibit increased surface membrane-bound amyloid precursor protein (mAPP) compared to age-matched controls.
• Activated platelets interact with the cerebrovascular endothelium, a process relevant to amyloid beta peptide (Abeta) deposit formation in AD.

Purpose of the Study:

• To investigate the interaction between platelets and cerebrovascular endothelial cells (BECs) in the context of Alzheimer's disease.
• To determine the role of endothelial cells and platelet-derived amyloid precursor protein (APP) in the formation of amyloidogenic deposits.

Main Methods:

• Primary human blood brain barrier endothelial cell (BEC) cultures from AD patients (AD-BEC) and age-matched controls (AM-BEC) were used.
• Human umbilical vein endothelial cells (HUVECs) served as a control cell type.
• Secretase-like activities (alpha, beta, gamma) and the penetration of platelet-released products (platelet factor 4, soluble APP) through endothelial layers were analyzed.

Main Results:

• Alpha and beta secretase-like activities were present in both AD-BEC and AM-BEC.
• Gamma secretase-like activity was detected exclusively in AD-BEC.
• Increased penetration of platelet-released factors was observed through AD-BEC compared to AM-BEC, with no penetration through HUVECs.

Conclusions:

• Cerebral vascular endothelial cells possess secretase-like activities that may contribute to amyloidogenesis.
• The interaction between platelets, their retained/released APP, and cerebral vascular endothelial cells appears to play a role in the formation of amyloidogenic deposits around cerebral vasculature in AD patients.