scholarly journals Caveolae, CD109, and endothelial cells as targets for treating Alzheimer's disease

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jeffrey Fessel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells

scholarly journals Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease

2020 ◽  
Vol 117 (41) ◽  
pp. 25800-25809 ◽  
Author(s):  
Shun-Fat Lau ◽  
Han Cao ◽  
Amy K. Y. Fu ◽  
Nancy Y. Ip
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Transcriptome Analysis ◽  
Cell Type ◽  
Angiogenic Growth Factors ◽  
Cellular Targets ◽  
Therapeutic Development ◽  
Single Nucleus ◽  
Cell Type Specific

Alzheimer’s disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation of cell type-specific responses and cellular heterogeneity in AD is required to provide precise molecular and cellular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis of 169,496 nuclei from the prefrontal cortical samples of AD patients and normal control (NC) subjects. Differential analysis shows that the cell type-specific transcriptomic changes in AD are associated with the disruption of biological processes including angiogenesis, immune activation, synaptic signaling, and myelination. Subcluster analysis reveals that compared to NC brains, AD brains contain fewer neuroprotective astrocytes and oligodendrocytes. Importantly, our findings show that a subpopulation of angiogenic endothelial cells is induced in the brain in patients with AD. These angiogenic endothelial cells exhibit increased expression of angiogenic growth factors and their receptors (i.e.,EGFL7,FLT1, andVWF) and antigen-presentation machinery (i.e.,B2MandHLA-E). This suggests that these endothelial cells contribute to angiogenesis and immune response in AD pathogenesis. Thus, our comprehensive molecular profiling of brain samples from patients with AD reveals previously unknown molecular changes as well as cellular targets that potentially underlie the functional dysregulation of endothelial cells, astrocytes, and oligodendrocytes in AD, providing important insights for therapeutic development.

scholarly journals Brain Endothelial Cells Synthesize Neurotoxic Thrombin in Alzheimer’s Disease

2010 ◽  
Vol 176 (4) ◽  
pp. 1600-1606 ◽  
Author(s):  
Xiangling Yin ◽  
Jill Wright ◽  
Trevor Wall ◽  
Paula Grammas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Brain Endothelial Cells

scholarly journals BACE-1 is expressed in the blood–brain barrier endothelium and is upregulated in a murine model of Alzheimer’s disease

2015 ◽  
Vol 36 (7) ◽  
pp. 1281-1294 ◽  
Author(s):  
Kavi Devraj ◽  
Slobodan Poznanovic ◽  
Christoph Spahn ◽  
Gerhard Schwall ◽  
Patrick N Harter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mouse Brain Endothelial Cells ◽  
Primary Mouse ◽  
Β Amyloid ◽  
Bace 1

Endothelial cells of the blood–brain barrier form a structural and functional barrier maintaining brain homeostasis via paracellular tight junctions and specific transporters such as P-glycoprotein. The blood–brain barrier is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer’s disease, current treatment approaches include inhibitors of BACE-1 (β-site of amyloid precursor protein cleaving enzyme), a proteinase generating neurotoxic β-amyloid. It is known that BACE-1 is highly expressed in endosomes and membranes of neurons and glia. We now provide evidence that BACE-1 is expressed in blood–brain barrier endothelial cells of human, mouse, and bovine origin. We further show its predominant membrane localization by 3D- dSTORM super-resolution microscopy, and by biochemical fractionation that further shows an abluminal distribution of BACE-1 in brain microvessels. We confirm its functionality in processing APP in primary mouse brain endothelial cells. In an Alzheimer’s disease mouse model we show that BACE-1 is upregulated at the blood–brain barrier compared to healthy controls. We therefore suggest a critical role for BACE-1 at the blood–brain barrier in β-amyloid generation and in vascular aspects of Alzheimer’s disease, particularly in the development of cerebral amyloid angiopathy.

Reduced glucose transporter-1 in brain derived circulating endothelial cells in mild Alzheimer’s disease patients

2018 ◽  
Vol 1678 ◽  
pp. 304-309 ◽  
Author(s):  
Petra Vogelsang ◽  
Lasse Melvaer Giil ◽  
Anders Lund ◽  
Christian A. Vedeler ◽  
Anagha P. Parkar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Glucose Transporter ◽  
Circulating Endothelial Cells ◽  
Glucose Transporter 1

scholarly journals Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer’s Disease

2016 ◽  
Vol 54 (4) ◽  
pp. 1373-1383 ◽  
Author(s):  
Marat A. Mukhamedyarov ◽  
Albert A. Rizvanov ◽  
Eduard Z. Yakupov ◽  
Andrey L. Zefirov ◽  
Andrey P. Kiyasov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Skin Fibroblasts ◽  
Transcriptional Analysis ◽  
Blood Lymphocytes ◽  
Potential Biomarker

P2-264: Oxysterols, Blood-Brain Barrier (BBB) and Alzheimer's Disease: in vitro studies on endothelial cells and pericytes

2011 ◽  
Vol 7 ◽  
pp. S396-S397
Author(s):  
Julien Saint-Pol ◽  
Elodie Vandenhaute ◽  
Marie-Christine Boucau ◽  
Lucie Dehouck ◽  
Roméo Cecchelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
In Vitro Studies ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease

2015 ◽  
Vol 36 (1) ◽  
pp. 216-227 ◽  
Author(s):  
Matthew R Halliday ◽  
Sanket V Rege ◽  
Qingyi Ma ◽  
Zhen Zhao ◽  
Carol A Miller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Late Onset ◽  
Density Lipoprotein ◽  
Brain Barrier ◽  
Lipoprotein Receptor ◽  
Apolipoprotein E4 ◽  
Blood Brain

The blood–brain barrier (BBB) limits the entry of neurotoxic blood-derived products and cells into the brain that is required for normal neuronal functioning and information processing. Pericytes maintain the integrity of the BBB and degenerate in Alzheimer’s disease (AD). The BBB is damaged in AD, particularly in individuals carrying apolipoprotein E4 ( APOE4) gene, which is a major genetic risk factor for late-onset AD. The mechanisms underlying the BBB breakdown in AD remain, however, elusive. Here, we show accelerated pericyte degeneration in AD APOE4 carriers >AD APOE3 carriers >non-AD controls, which correlates with the magnitude of BBB breakdown to immunoglobulin G and fibrin. We also show accumulation of the proinflammatory cytokine cyclophilin A (CypA) and matrix metalloproteinase-9 (MMP-9) in pericytes and endothelial cells in AD ( APOE4 > APOE3), previously shown to lead to BBB breakdown in transgenic APOE4 mice. The levels of the apoE lipoprotein receptor, low-density lipoprotein receptor-related protein-1 (LRP1), were similarly reduced in AD APOE4 and APOE3 carriers. Our data suggest that APOE4 leads to accelerated pericyte loss and enhanced activation of LRP1-dependent CypA–MMP-9 BBB-degrading pathway in pericytes and endothelial cells, which can mediate a greater BBB damage in AD APOE4 compared with AD APOE3 carriers.

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