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

被引:32
作者
Davies, TA
Long, HJ
Eisenhauer, PB
Hastey, R
Cribbs, DH
Fine, RE
Simons, ER
机构
[1] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[3] Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA
[4] Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA 92697 USA
来源
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS | 2000年 / 7卷 / 03期
关键词
Alzheimer's disease; blood brain barrier; endothelial cells; platelets; secretases; amyloid peptide;
D O I
10.3109/13506120009146830
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amyloid precursor protein (A beta PP) processing results in generation of amyloid beta peptide (A beta) which deposits in the brain parenchyma and cerebrovasculature of patients with Alzheimer b disease (AD). Evidence that the vascular deposits derive in part from A beta PP fragments originating from activated platelets includes findings that individuals who have had multiple small strokes have a higher prevalence of AD compared to individual's who have taken antiplatelet drugs. Thus, determination of whether platelet A beta PP 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 transmembrane-bound A beta PP (mA beta PP) than control platelets. We report here that this mA beta PP can be cleaved to A beta-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 mA beta PP, cleave fluorescein-tagged surface proteins, including mA beta PP, resulting in passage to the BEC layer. The data confirm that BEC contribute to processing of platelet derived mA beta PP and show that the processing yields A beta containing fragments which could potentially contribute to cerebrovascular A beta deposition.
引用
收藏
页码:153 / 165
页数:13
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