scholarly journals Relative importance of redox buffers GSH and NAD (P)H in age‐related neurodegeneration and Alzheimer disease‐like mouse neurons

Aging Cell ◽  
2014 ◽  
Vol 13 (4) ◽  
pp. 631-640 ◽  
Author(s):  
Debolina Ghosh ◽  
Kelsey R. Levault ◽  
Gregory J. Brewer
Keyword(s):  
Alzheimer Disease ◽  
Relative Importance ◽  
Age Related ◽  
Redox Buffers

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease

2018 ◽  
Vol 15 (14) ◽  
pp. 1354-1360 ◽  
Author(s):  
Ping-Song Chou ◽  
Yi-Hui Kao ◽  
Meng-Ni Wu ◽  
Mei-Chuan Chou ◽  
Chun-Hung Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Alzheimer Disease ◽  
Rating Scale ◽  
Vital Role ◽  
Independent Effect ◽  
Cerebral White Matter ◽  
Clinical Dementia Rating ◽  
White Matter Changes ◽  
Age Related ◽  
The Mean

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Regional Age-Related Atrophy After Screening for Preclinical Alzheimer Disease

2021 ◽  
Author(s):  
Lauren N. Koenig ◽  
Pamela LaMontagne ◽  
Matthew F. Glasser ◽  
Randall Bateman ◽  
David Holtzman ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Age Related

scholarly journals Cytochemical Demonstration of Oxidative Damage in Alzheimer Disease by Immunochemical Enhancement of the Carbonyl Reaction with 2,4-Dinitrophenylhydrazine

1998 ◽  
Vol 46 (6) ◽  
pp. 731-735 ◽  
Author(s):  
Mark A. Smith ◽  
Lawrence M. Sayre ◽  
Vernon E. Anderson ◽  
Peggy L.R. Harris ◽  
M. Flint Beal ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Oxidative Damage ◽  
Peroxidation Of Lipids ◽  
Bulk Analysis ◽  
Age Related ◽  
Cytochemical Demonstration ◽  
Highly Sensitive ◽  
Metal Catalyzed ◽  
Specific Oxidation ◽  
Cytochemical Technique

Formation of carbonyls derived from lipids, proteins, carbohydrates, and nucleic acids is common during oxidative stress. For example, metal-catalyzed, “site-specific” oxidation of several amino acid side-chains produces aldehydes or ketones, and peroxidation of lipids generates reactive aldehydes such as malondialdehyde and hydroxynonenal. Here, using in situ 2,4-dinitrophenylhydrazine labeling linked to an antibody system, we describe a highly sensitive and specific cytochemical technique to specifically localize biomacromolecule-bound carbonyl reactivity. When this technique was applied to tissues from cases of Alzheimer disease, in which oxidative events including lipoperoxidative, glycoxidative, and other oxidative protein modifications have been reported, we detected free carbonyls not only in the disease-related intraneuronal lesions but also in other neurons. In marked contrast, free carbonyls were not found in neurons or glia in age-matched control cases. Importantly, this assay was highly specific for detecting disease-related oxidative damage because the site of oxidative damage can be assessed in the midst of concurrent age-related increases in free carbonyls in vascular basement membrane that would contaminate biochemical samples subjected to bulk analysis. These findings demonstrate that oxidative imbalance and stress are key elements in the pathogenesis of Alzheimer disease.

scholarly journals Age-Related Changes of the Neurovascular Unit in the Cerebral Cortex of Alzheimer Disease Mouse Models: A Neuroanatomical and Molecular Study

2019 ◽  
Vol 78 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Alessandro Giuliani ◽  
Sandra Sivilia ◽  
Vito Antonio Baldassarro ◽  
Marco Gusciglio ◽  
Luca Lorenzini ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Alzheimer Disease ◽  
Mouse Models ◽  
Neurovascular Unit ◽  
Molecular Study ◽  
Age Related ◽  
Age Related Changes

Dating Quaternary Fault Scarps Formed in Alluvium Using Morphologic Parameters

1984 ◽  
Vol 22 (3) ◽  
pp. 300-313 ◽  
Author(s):  
Larry Mayer
Keyword(s):  
Diffusion Equation ◽  
Discriminant Function ◽  
Linear Discriminant Function ◽  
Relative Importance ◽  
Linear Discriminant ◽  
Age Related ◽  
Variation Data ◽  
Morphologic Variation ◽  
Fault Scarps ◽  
Age Estimates

Ages of fault scarps, as well as those other types of transport-limited slopes, can be estimated by comparing their morphology with the morphology of scarps of known age. Age estimates are derived by fitting the scarp profiles to synthetic profiles generated using a diffusion equation or, alternatively, by classification using a linear discriminant function. The usefulness of morphology-derived age estimates depends on the relative importance of non-age-related morphologic variation. Data from more than 200 scarp profiles demonstrate that morphologic variation not related to scarp age can introduce significant uncertainties into morphology-derived age estimates.

scholarly journals The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration

2021 ◽  
Vol 15 ◽  
Author(s):  
Lay Khoon Too ◽  
Nicholas Hunt ◽  
Matthew P. Simunovic
Keyword(s):  
Risk Factors ◽  
Alzheimer Disease ◽  
Bacterial Meningitis ◽  
Neurodegenerative Diseases ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Similar Process ◽  
Complex Nature ◽  
Brain Functions ◽  
Age Related

Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD. Acute neurological infections, such as Bacterial Meningitis (BM), trigger inflammatory events that permanently change how the brain functions, leading to lasting cognitive impairment. Neuroinflammation likewise is a known pathological event that occurs in the early stages of chronic age-related neurodegenerative diseases AD and AMD and might be triggered as a parainfectious event. To date, at least 16 microbial pathogens have been linked to the development of AD; on the other hand, investigation of a microbe-AMD relationship is in its infancy. This mini-review article provides a synthesis of existing evidence indicating a contribution of parainfection in the aetiology of AD and of emerging findings that support a similar process in AMD. Subsequently, it describes the major immunopathological mechanisms that are common to BM and AD/AMD. Together, this evidence leads to our proposal that both AD and AMD may have an infectious aetiology that operates through a dysregulated inflammatory response, leading to deleterious outcomes. Last, it draws fresh insights from the existing literature about potential therapeutic options for BM that might alleviate neurological disruption associated with infections, and which could, by extension, be explored in the context of AD and AMD.

scholarly journals Oxidative stress-induced mitochondrial failure and vasoactive substances as key initiators of pathology favor the reclassification of Alzheimer Disease as a vasocognopathy

Nova ◽  
2008 ◽  
Vol 6 (10) ◽  
pp. 170
Author(s):  
Gjumrakch Aliev ◽  
Joséph Charles Lamanna ◽  
Ludis Morales Álvarez ◽  
Mark Eric Obrenovich ◽  
Gerardo Jesús Pacheco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Pyramidal Neurons ◽  
Cell Damage ◽  
Cell Types ◽  
Vascular Wall ◽  
Chronic Injury ◽  
Mtdna Deletions ◽  
Age Related ◽  
Brain Parenchymal

Alzheimer disease and cerebrovascular accident are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. Hypoperfusion is associated with oxidative imbalance, largely due to reactive oxygen species, which is associated with other age-related degenerative disorders. Recent evidence indicates that a chronic injury stimulus induces the hypoperfusion seen in the microcirculation of vulnerable regions of the brain. This leads to energy failure, manifested by damaged mitochondrial ultrastructure. Mitochondrial derangements lead to the formation of a large number of electron-dense, ¿hypoxic¿ mitochondria and cause the overproduction of mitochondrial DNA (mtDNA) deletions, which is most likely due to double stranded breaks. Additionally, these mitochondrial abnormalities coexist with increased redox metal activity, lipid peroxidation, and RNA oxidation, all of which are well established features of Alzheimer disease pathology, prior to the appearance of amyloid b deposition. Alzheimer disease, oxidative stress occurs within various cellular compartments and within certain cell types more than others, namely the vascular endothelium, which is associated with atherosclerotic damage, as well as in pyramidal neurons and glia. Interestingly, these vulnerable cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels. This evidence strongly suggests that chronic hypoperfusion induces the accumulation of the oxidative stress products. Furthermore, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We, therefore, conclude that chronic hypoperfusion is a key initiator of oxidative stress in various brain parenchymal cells, and the mitochondria appear to be primary targets for brain damage in Alzheimer disease. In this manuscript, we outline a role for the continuous accumulation of oxidative stress products, such as an abundance of nitric oxide products (via the overexpression of inducible and/or neuronal NO synthase (iNOS and nNOS respectively) and peroxynitrite accumulation, as secondary but accelerating factors compromising the blood brain barrier (BBB). If this turns out to be the case, pharmacological interventions that target chronic hypoperfusion might ameliorate the key features of dementing neurodegeneration.

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