Amyloid-β Decreases Nitric Oxide Production in Cultured Retinal Neurons: A Possible Mechanism for Synaptic Dysfunction in Alzheimer’s Disease?

2010 ◽  
Vol 36 (1) ◽  
pp. 163-169 ◽  
Author(s):  
Leandro T. Oliveira ◽  
Paulo Roberto Louzada ◽  
Fernando G. de Mello ◽  
Sérgio T. Ferreira
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Nitric Oxide Production ◽  
Retinal Neurons ◽  
Oxide Production

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

scholarly journals Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss

2018 ◽  
Vol 39 (4) ◽  
pp. 758-772 ◽  
Author(s):  
Santiago V. Salazar ◽  
Timothy O. Cox ◽  
Suho Lee ◽  
A. Harrison Brody ◽  
Annabel S. Chyung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Disease Risk Factor

scholarly journals Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3261
Author(s):  
Xiao Liu ◽  
Qian Zhou ◽  
Jia-He Zhang ◽  
Xiaoying Wang ◽  
Xiumei Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Disease Model ◽  
Amyloid Β ◽  
Brain Lesions ◽  
Synaptic Dysfunction ◽  
Synaptic Loss ◽  
And Function ◽  
The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

scholarly journals Amyloid β-induced Changes in Nitric Oxide Production and Mitochondrial Activity Lead to Apoptosis

2004 ◽  
Vol 279 (48) ◽  
pp. 50310-50320 ◽  
Author(s):  
Uta Keil ◽  
Astrid Bonert ◽  
Celio A. Marques ◽  
Isabel Scherping ◽  
Jörg Weyermann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amyloid Β ◽  
Mitochondrial Activity ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Induced Changes

scholarly journals The glymphatic system and its role in the development of Alzheimer’s disease

2021 ◽  
Vol 8 (3) ◽  
pp. 14-21
Author(s):  
S. V. Vorobʼev ◽  
S. N. Yanishevskij
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Picture ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
Comprehensive Analysis ◽  
Synaptic Dysfunction ◽  
Glymphatic System ◽  
Neurodegenerative Pathology ◽  
The Brain

One of the main concepts explaining the development of Alzheimer’s disease is currently the amyloid theory. It was reliably established that the accumulation of the pathological protein amyloid β provokes the launch of a number of pathochemical reactions that ultimately lead to the development of synaptic dysfunction and the formation of cognitive disorders. The protein amyloid β is also synthesized in the brain of people who do not suffer from neurodegenerative pathology. Normally, it is actively removed from the brain. However, the exact mechanisms for maintaining its clearance are not established. The recently discovered glymphatic system claims to be such a component. The present review provides a comprehensive analysis of suggestions that the development of glymphatic system dysfunction contributes to the accumulation of amyloid β and the development of the clinical picture of Alzheimer›s disease.

scholarly journals Cerebral hypoperfusion is a late pathological event in the course of Alzheimer's disease

2021 ◽  
Author(s):  
Khazar Ahmadi ◽  
Joana B. Pereira ◽  
David Berron ◽  
Jacob Vogel ◽  
Silvia Ingala ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Cerebral Hypoperfusion ◽  
Synaptic Dysfunction ◽  
Early Event ◽  
Preclinical Phase ◽  
Disease Progression Modeling

Although several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, positron emission tomography, and biomarkers of cerebrospinal fluid, we investigated the associations between CBF and the key mechanisms in AD including amyloid-β (Aβ) and tau pathology, synaptic dysfunction and axonal degeneration. Further, we applied a disease progression modeling to characterize the temporal sequence of different AD biomarkers. Lower perfusion was observed in the temporo-occipito-parietal regions in the Aβ-positive cognitively impaired compared to both the Aβ-positive and Aβ-negative cognitively unimpaired individuals. In participants along the AD spectrum (those with Aβ pathology regardless of their cognitive status), CBF was inversely associated with tau and synaptic dysfunction, but not Aβ in similar cortical regions. Moreover, the disease progression modeling revealed that CBF disruption followed the abnormality of biomarkers of Aβ, tau and brain atrophy. These findings indicate that tau tangles and synaptic degeneration are more closely connected with CBF changes rather than Aβ pathology. This supports the notion that hypoperfusion is not an early event associated with the build-up of Aβ during the preclinical phase of AD.

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