The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
Astrocytes are fundamental for brain homeostasis and are at the fulcrum of neurological diseases including Alzheimer's disease (AD). Here, we monitored changes in astroglia morphology throughout the age‐dependent progression of AD. We used an immunohistochemical approach that allows us to determine the domain of glial cytoskeleton, by measuring the surface, volume, and the relationship between astrocytes...
Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of β‐amyloid (Aβ) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Aβ and Aβ deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a...
Intracerebral accumulation of amyloid‐β (Aβ) leading to Aβ plaque formation, is the main hallmark of Alzheimer's disease and might be caused by defective Aβ‐clearance. We previously found primary human astrocytes and microglia able to bind and ingest Aβ1‐42 in vitro, which appeared to be limited by Aβ1‐42 fibril formation. We now confirm that astrocytic Aβ‐uptake depends on size and/or composition...
Despite the phagocytic machinery available to microglia the aberrant amyloid proteins produced during Alzheimer's and prion disease, amyloid‐β and PrPSc, are inefficiently cleared. We have shown that microglia in the ME7 model of prion disease show morphological evidence of activation, synthesize low levels of pro‐inflammatory cytokines and are primed to produce exaggerated responses to subsequent...
Microglia activation is central to the neuroinflammation associated with neurological and neurodegenerative diseases, particularly because activated microglia are often a source of proinflammatory cytokines. Despite decade‐long research, the molecular cascade of proinflammatory transformation of microglia in vivo remains largely elusive. Here, we report increased β‐catenin expression, a central intracellular...
White matter pathology has been documented in the brains of familial Alzheimer's disease (FAD)‐afflicted individuals during presymptomatic and preclinical stages of AD. How these defects in myelination integrity arise and what roles they may play in AD pathophysiology have yet to be fully elucidated. We previously demonstrated that triple‐transgenic AD (3xTg‐AD) mice, which harbor the human amyloid...
Inflammatory responses mediated by glial cells play a critical role in many pathological situations related to neurodegeneration such as Alzheimer's disease. Tissue plasminogen activator (tPA) is a serine protease which best‐known function is fibrinolysis, but it is also involved in many other physiological and pathological events as microglial activation. Here, we found that tPA is required for Aβ‐mediated...
The ϵ4 allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for late‐onset Alzheimer's disease (AD), and affects clinical outcomes of chronic and acute brain damages. The mechanisms by which apoE affect diverse diseases and disorders may involve modulation of the glial response to various types of brain damage. We examined glial activation in a mouse model where each of...
Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 transgenic (AD) mice at different ages. Mice were studied shortly after the last BrdU...
It is well accepted that CNS inflammation has a role in the progression of chronic neurodegenerative disease, although the mechanisms through which this occurs are still unclear. The inflammatory response during most chronic neurodegenerative disease is dominated by the microglia and mechanisms by which these cells contribute to neuronal damage and degeneration are the subject of intense study. More...
Myelin loss is frequently observed in human Alzheimer's disease (AD) and may constitute to AD‐related cognitive decline. A potential source to repair myelin defects are the oligodendrocyte progenitor cells (OPCs) present in an adult brain. However, until now, little is known about the reaction of these cells toward amyloid plaque deposition neither in human AD patients nor in the appropriate mouse...
Defective clearance of the amyloid‐β peptide (Aβ) from the brain is considered a strong promoter in Alzheimer's disease (AD) pathogenesis. Astrocytes and microglia are important mediators of Aβ clearance and Aβ aggregation state and the presence of amyloid associated proteins (AAPs), such as Apolipoproteins E and J (ApoE and ApoJ), may influence Aβ clearance by these cells. Here we set out to investigate...
β‐Amyloid (Aβ) oligomers initiate synaptotoxicity following their interaction with the plasma membrane. Several proteins including metabotropic glutamate type 5 receptors (mGluR5s) contribute to this process. We observed an overexpression of mGluR5s in reactive astrocytes surrounding Aβ plaques in brain sections from an Alzheimer's disease mouse model. In a simplified cell culture system, using immunocytochemistry...
Apolipoprotein E (apoE) is well known as a regulator of cholesterol homeostasis, and is increasingly recognized to play a prominent role in the modulation of innate immune response, including cell‐to‐cell communication and migration. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder characterized by neuroinflammation that appears to be an important component of the pathophysiology...
Objectives and experimental design Cerebella of young adults, elderly adults, and patients with Alzheimer's disease (AD) (with and without cerebellar amyloid deposits) were studied by Golgi staining and glial fibrillary acid protein (GFAP) immunocytochemical methods. Observations Three subtypes of Golgi epithelial cells and nine subtypes of stellate neuroglia (both normal and hypertrophic) were defined...
Oxidative stress plays an important role in the progression of Alzheimer's disease (AD) and other neurodegenerative conditions. Glutathione (GSH), the major antioxidant in the central nervous system, is primarily synthesized and released by astrocytes. We determined if β‐amyloid (Aβ42), crucially involved in Alzheimer's disease, affected GSH release. Monomeric Aβ (mAβ) stimulated GSH release from...
Genome‐wide expression profiling technology has resulted in detailed transcriptome data for a wide range of tissues, conditions and diseases. In neuroscience, expression datasets were mostly generated using whole brain tissue samples, resulting in data from a mixture of cell types, including glial cells and neurons. Over the past few years, a rapidly increasing number of expression profiling studies...
One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid β‐protein (Aβ) in the brain. Aβ accumulation seems to arise from an imbalance between Aβ production and clearance. Neprilysin (NEP) and insulin‐degrading enzyme (IDE) are the important Aβ‐degrading enzymes in the brain, and deficits in their expression may promote Aβ deposition in patients with sporadic...
Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [11C]‐R‐PK11195 has been challenging due to the limitations of the ligand. In...
While histological changes in microglia have long been recognized as a pathological feature of Alzheimer's disease (AD), recent genetic association studies have also strongly implicated microglia in the etiology of the disease. Coding and noncoding polymorphisms in several genes expressed in microglia—including APOE, TREM2, CD33, GRN, and IL1RAP—alter AD risk, and therefore could be considered as...
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.