Tubuloreticular structures in microglial cells, pericytes and endothelial cells in Alzheimer's disease

1992 ◽  
Vol 83 (6) ◽  
pp. 653-658 ◽  
Author(s):  
Jerzy Wegiel ◽  
Henryk M. Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Microglial Cells ◽  
Tubuloreticular Structures

Advanced glycation end products co-localized with astrocytes and microglial cells in Alzheimer's disease brain

1998 ◽  
Vol 95 (6) ◽  
pp. 555-558 ◽  
Author(s):  
Akinori Takeda ◽  
Takeshi Yasuda ◽  
Toshio Miyata ◽  
Yoji Goto ◽  
Masakazu Wakai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Advanced Glycation End Products ◽  
Microglial Cells ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

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

Oxidative signalling and inflammatory pathways in Alzheimer's disease

2001 ◽  
Vol 67 ◽  
pp. 141-149 ◽  
Author(s):  
Ian Anderson ◽  
Christy Adinolfi ◽  
Susan Doctrow ◽  
Karl Huffman ◽  
Ken A. Joy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Cell ◽  
Amyloid Peptide ◽  
Microglial Cells ◽  
Amino Acid Form ◽  
Factor Α ◽  
Molecular Components ◽  
And Oxidative Stress

It is well established that inflammation and oxidative stress are key components of the pathology of Alzheimer's disease (AD), but how early in the pathological cascade these processes are involved or which specific molecular components are key, has not been fully elucidated. This paper describes the pharmacological approach to understand the molecular components of inflammation and oxidative stress on the activation of microglial cells and neuronal cell viability. We have shown that activation of microglia with the 42-amino-acid form of the ϐ-amyloid peptide (Aϐ42) activates the production of cyclooxygenase-2, the inducible form of nitric oxide synthase and tumour necrosis factor-α and there appears to be little interactive feedback between these three mediators. Moreover, we explore the effects of a series of salen-manganese complexes, EUK-8, -134 and -189, which are known to possess both superoxide and catalase activity. These compounds are able to protect cells from insults produced by hydrogen peroxide or peroxynitrite. Moreover, EUK-134 was also able to limit the output of prostaglandin E2 from activated microglial cells. The mechanisms underlying these effects are discussed. Together, these data support a pivotal role for oxidative stress and inflammation as key mediators of the pathological cascade in AD and provide some ideas about possible therapeutic targets.

Activated Microglial Cells Are Colocalized With Perivascular Deposits of Amyloid-β Protein in Alzheimer’s Disease Brain

Stroke ◽  
1997 ◽  
Vol 28 (10) ◽  
pp. 1948-1950 ◽  
Author(s):  
Toshiki Uchihara ◽  
Haruhiko Akiyama ◽  
Hiromi Kondo ◽  
Kenji Ikeda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Microglial Cells ◽  
Amyloid Β Protein ◽  
Β Protein

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.

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