scholarly journals Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 199
Author(s):  
Donald J. Alcendor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethnic Minorities ◽  
Ethnic Disparities ◽  
Cerebral Hypoperfusion ◽  
Cerebral Vascular Disease ◽  
Endothelin 1 ◽  
The Impact ◽  
Cerebral Vascular

Alzheimer’s disease (AD) and related dementias disproportionately impact racial and ethnic minorities. The racial and ethnic disparities in AD could be explained by differences in cerebral vascular disease pathology. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide that regulates smooth muscle, endothelial cell, and pericyte contractions that may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, ET-1 may result in neuronal injury contributing to the pathology of AD. Upregulation of the ET-1 system has been observed in African Americans when compared with non-Hispanic Whites. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. Targeting of the ET-1 system as a therapeutic intervention that could impact AD progression also needs further study. Dysregulation of ET-1 in Hispanic/Latino populations largely have been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also needs further investigation. In this review, I examine how AD effects underserved minority populations and how dysregulation of the ET-1 system specifically predisposes ethnic minorities to AD. In addition, I examine the molecular interactions of the ET-1 system and amyloid beta, the role the ET-1 system in neurodegeneration, potential therapeutics for ET-1 dysregulation, and the impact on AD progression.

scholarly journals Advancing Alzheimer’s Disease Care and Services Among Racial and Ethnic Minorities

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 745-745
Author(s):  
Lenora Smith ◽  
Roland Thorpe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African American ◽  
Ethnic Minorities ◽  
Health Care Expenditures ◽  
Racial And Ethnic Minorities ◽  
Care Services ◽  
Study Results ◽  
Using Data ◽  
The Impact

Abstract Research shows consistent and adverse disparities among racial and ethnic minorities compared to non-Hispanic Whites in the prevalence and incidence of Alzheimer’s disease, mortality, participation in clinical trials, use of medications and other interventions, health care expenditures, and quality-of-life outcomes. The literature suggests numerous underlying causes, including factors related to measurement of the disease, genetics, socioeconomic factors, cultural differences, lack of culturally competent interventions, and discrimination in services and care. Although these disparities are well known, little is known about the effectiveness of various strategies to address these differences within the context of Alzheimer’s disease services and care. This symposium aims to contribute to this knowledge. The first presentation examines the role of race with marital status and risk for dementia using data from the Health and Retirement Study. Results suggest differences for unmarried White and unmarried older adults of color, which can inform dementia care services. The second presentation highlights the opportunities and challenges of facilitating cognitive impairment screenings among African American congregations. The third presentation introduces attitudes about brain donation among African American research participants and suggestions to increase involvement. The symposium concludes with a presentation on hearing care disparities in dementia with practical recommendations on how to close this gap in hearing care. The findings from these papers contribute significantly to the impact of ethnoracial differences in dementia and the need to include more diverse populations in ADRD research to promote equity. Alzheimer’s Disease Research Interest Group Sponsored Symposium.

Neuropathological Assessments: Discussion

1997 ◽  
Vol 9 (S1) ◽  
pp. 269-272
Author(s):  
Barry Reisberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Disease ◽  
Original Work ◽  
Cerebral Vascular Disease ◽  
Similar Percentage ◽  
Cerebral Vascular

Reisberg: I would like to summarize very briefly. In the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study, one third of patients with Alzheimer's disease (AD) had concomitant cerebral vascular disease. This finding supports the original work of Tomlinson and Blessed, who indicated a similar percentage of patients with AD also had mixed cerebral vascular disease upon neuropathologic examination.

scholarly journals The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Holly C. Hunsberger ◽  
Priyanka D. Pinky ◽  
Warren Smith ◽  
Vishnu Suppiramaniam ◽  
Miranda N. Reed
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synapse Formation ◽  
Late Onset ◽  
Therapeutic Interventions ◽  
Memory Decline ◽  
Current Therapies ◽  
Ε4 Allele ◽  
The Impact

Abstract Alzheimer’s disease (AD) is the leading cause of dementia affecting almost 50 million people worldwide. The ε4 allele of Apolipoprotein E (APOE) is the strongest known genetic risk factor for late-onset AD cases, with homozygous APOE4 carriers being approximately 15-times more likely to develop the disease. With 25% of the population being APOE4 carriers, understanding the role of this allele in AD pathogenesis and pathophysiology is crucial. Though the exact mechanism by which ε4 allele increases the risk for AD is unknown, the processes mediated by APOE, including cholesterol transport, synapse formation, modulation of neurite outgrowth, synaptic plasticity, destabilization of microtubules, and β-amyloid clearance, suggest potential therapeutic targets. This review will summarize the impact of APOE on neurons and neuronal signaling, the interactions between APOE and AD pathology, and the association with memory decline. We will then describe current treatments targeting APOE4, complications associated with the current therapies, and suggestions for future areas of research and treatment.

Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress

2012 ◽  
Vol 385 (10) ◽  
pp. 953-959 ◽  
Author(s):  
Hyun Ah Kim ◽  
Alyson A. Miller ◽  
Grant R. Drummond ◽  
Amanda G. Thrift ◽  
Thiruma V. Arumugam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Cerebral Hypoperfusion ◽  
And Oxidative Stress

scholarly journals Increased Cerebral Vascular Reactivity in the Tau Expressing rTg4510 Mouse: Evidence against the Role of Tau Pathology to Impair Vascular Health in Alzheimer's Disease

2015 ◽  
Vol 35 (3) ◽  
pp. 359-362 ◽  
Author(s):  
Jack A Wells ◽  
Holly E Holmes ◽  
James M O'Callaghan ◽  
Niall Colgan ◽  
Ozama Ismail ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Reactivity ◽  
Vascular Health ◽  
Tau Pathology ◽  
Vascular Abnormalities ◽  
Rtg4510 Mouse ◽  
Cortical Regions ◽  
Cerebral Vascular

Vascular abnormalities are a key feature of Alzheimer's disease (AD). Imaging of cerebral vascular reactivity (CVR) is a powerful tool to investigate vascular health in clinical populations although the cause of reduced CVR in AD patients is not fully understood. We investigated the specific role of tau pathology in CVR derangement in AD using the rTg4510 mouse model. We observed an increase in CVR in cortical regions with tau pathology. These data suggest that tau pathology alone does not produce the clinically observed decreases in CVR and implicates amyloid pathology as the dominant etiology of impaired CVR in AD patients.

scholarly journals Oxysterols Present in Alzheimer’s Disease Braininduce Synaptoxicity by Activating Astrocytes: A Major Role for Lipocalin-2

2020 ◽  
Author(s):  
Erica Staurenghi ◽  
Valentina Cerrato ◽  
Paola Gamba ◽  
Gabriella Testa ◽  
Serena Giannelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholesterol Metabolism ◽  
Reactive Astrocytes ◽  
Cholesterol Oxidation ◽  
Neuronal Cultures ◽  
Lipocalin 2 ◽  
Brain Cholesterol ◽  
The Impact

Abstract Background: Among Alzheimer’s disease (AD) brain hallmarks, the presence of reactive astrocytes was demonstrated to correlate with neuronal loss and cognitive deficits. Evidence indeed supports the role of reactive astrocytes as mediators of changes in neurons, including synapses. However, the complexity and the outcomes of astrocyte reactivity are far from being completely elucidated. Another key role in AD pathogenesis is played by alterations in brain cholesterol metabolism. Oxysterols (cholesterol oxidation products) are crucial for brain cholesterol homeostasis, and we previously demonstrated that changes in the brain levels of various oxysterols correlate with AD progression. Moreover, oxysterols have been shown to contribute to various pathological mechanisms involved in AD pathogenesis.In order to deepen the role of oxysterols in AD, we investigated whether they could contribute to astrocyte reactivity, and consequently impact on neuronal health.Methods: Mouse primary astrocyte cultures were used to test the effect of two oxysterol mixtures, that represent the oxysterol composition respectively of mild or severe AD brains, on astrocyte morphology, markers of reactivity, and secretion profile. Co-culture experiments were performed to investigate the impact of oxysterol-treated astrocytes on neurons. Neuronal cultures were exposed to astrocyte conditioned media (ACM) deprived of lipocalin-2 (Lcn2) to investigate the contribution of this mediator to synaptotoxicity.Results: Results showed that oxysterols induce a clear morphological change in astrocytes, accompanied by the upregulation of some reactive astrocyte markers, including Lcn2. Moreover, ACM analysis revealed a significant increase in the release of Lcn2, cytokines, and chemokines in response to oxysterols. A significant reduction of postsynaptic density protein 95 (PSD95) and a concurrent increase in cleaved caspase-3 protein levels have been demonstrated in neurons co-cultured with oxysterol-treated astrocytes, pointing out that mediators released by astrocytes have an impact on neurons. Among these mediators, Lcn2 has been demonstrated to play a major role on synapses, affecting neurite morphology and decreasing dendritic spine density. Conclusions: These data demonstrated that oxysterols present in the AD brain promote astrocyte reactivity, determining the release of several mediators that affect neuronal health and synapses. Lcn2 has been shown to exert a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.

Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles

2020 ◽  
Vol 16 (13) ◽  
pp. 1216-1229 ◽  
Author(s):  
Anurag K. Singh ◽  
Gaurav Mishra ◽  
Anand Maurya ◽  
Rajendra Awasthi ◽  
Komal Kumari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Tau Pathology ◽  
Functional Roles ◽  
Age Related ◽  
Β Amyloid ◽  
The Impact ◽  
Neuronal Stress

: Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on β-amyloid plaques and tau pathology in Alzheimer’s disease.

scholarly journals The English (H6R) Mutation of the Alzheimer’s Disease Amyloid-β Peptide Modulates Its Zinc-Induced Aggregation

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 961
Author(s):  
Sergey P. Radko ◽  
Svetlana A. Khmeleva ◽  
Dmitry N. Kaluzhny ◽  
Olga I. Kechko ◽  
Yana Y. Kiseleva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Random Coil ◽  
Amyloid Β Peptide ◽  
Zinc Ions ◽  
Aβ Aggregation ◽  
Aβ42 Peptide ◽  
The Impact ◽  
Induced Aggregation

The coordination of zinc ions by histidine residues of amyloid-beta peptide (Aβ) plays a critical role in the zinc-induced Aβ aggregation implicated in Alzheimer’s disease (AD) pathogenesis. The histidine to arginine substitution at position 6 of the Aβ sequence (H6R, English mutation) leads to an early onset of AD. Herein, we studied the effects of zinc ions on the aggregation of the Aβ42 peptide and its isoform carrying the H6R mutation (H6R-Aβ42) by circular dichroism spectroscopy, dynamic light scattering, turbidimetric and sedimentation methods, and bis-ANS and thioflavin T fluorescence assays. Zinc ions triggered the occurrence of amorphous aggregates for both Aβ42 and H6R-Aβ42 peptides but with distinct optical properties. The structural difference of the formed Aβ42 and H6R-Aβ42 zinc-induced amorphous aggregates was also supported by the results of the bis-ANS assay. Moreover, while the Aβ42 peptide demonstrated an increase in the random coil and β-sheet content upon complexing with zinc ions, the H6R-Aβ42 peptide showed no appreciable structural changes under the same conditions. These observations were ascribed to the impact of H6R mutation on a mode of zinc/peptide binding. The presented findings further advance the understanding of the pathological role of the H6R mutation and the role of H6 residue in the zinc-induced Aβ aggregation.

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