Abstract
Cerebral Amyloid Angiopathy (CAA) occurs commonly among the elderly and almost invariably in patients with Alzheimer’s Disease (AD). The β-amyloid peptides (Aβ) are produced via the amy-loidogenic processing of β-Amyloid Precursor Protein (APP) by β-secretase-1 (BACE1) and γ- secretase. Vascular endothelial cells are lately shown to possess the molecular machinery of Aβ production, which might participate in the development of CAA. Hypercholesterolemia is considered a risk factor for AD, whereas less is known if cholesterol may modulate endothelial Aβ production. In the present study we verified the amyloidogenic capability of Human Umbilical Vein Endothelial Cells (HUVECs) in vitro and explored the effect of cholesterol exposure on their amy-loidogenic potential. Cholesterol treatments at 12.5 and 25 mg/dL significantly elevated APP, BACE1 and APP β-CTF protein levels and β-site APP cleavage activity in cell lysates, and Aβ40 levels in culture medium. However, coincubation with cholesterol at 50 and 100 mg/dL attenuated the viability of the cultured cells and diminished their amyloidogenic capability. These findings suggest that high cholesterol exposure is stressful to vascular endothelial cells, and at a certain dosage range can promote an amyloidogenic response in these cells.
Highlights
Cerebral amyloidosis is a pathological condition caused by the deposition of the β-amyloid peptides (Aβ) in the extracellular matrix and vascular wall in the central nervous system, referred to as parenchymal amyloid plaques and Cerebral Amyloid Angiopathy (CAA), respectively [1] [2]
Amyloid plaques and CAA are among the definitive neuropathological lesions of dementia of the Alzheimer’s Disease (AD) and vascular types [3]-[5], both types of amyloidosis can be seen in the brain of non-demented elderly [6]-[13]
To check the expression of amyloidogenic proteins biochemically, Human Umbilical Vein Endothelial Cells (HUVECs) lysates were blotted in parallel with human cortical lysates
Summary
Cerebral amyloidosis is a pathological condition caused by the deposition of the β-amyloid peptides (Aβ) in the extracellular matrix and vascular wall in the central nervous system, referred to as parenchymal amyloid plaques and Cerebral Amyloid Angiopathy (CAA), respectively [1] [2]. Amyloid plaques and CAA are among the definitive neuropathological lesions of dementia of the Alzheimer’s Disease (AD) and vascular types [3]-[5], both types of amyloidosis can be seen in the brain of non-demented elderly [6]-[13]. Along with Aβ deposits, parenchymal and vascular amyloid pathology may coexist with degenerative and reactive cellular changes, including neuronal and vascular cell loss, neuritic dystrophy and glial activation [14]-[19]. Enhanced BACE1 expression is identified microscopically in dystrophic axons around neuritic and angiopathic Aβ deposition [18] [31]-[34]
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