Vascular Dysfunction in Alzheimer’s Disease: Alterations in the Plasma Contact and Fibrinolytic Systems

Badimon, Ana; Torrente, Daniel; Norris, Erin H.

doi:10.3390/ijms24087046

Cited by 10 publications

(7 citation statements)

References 127 publications

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“…Moreover, plasma kallikrein cleaves HMWK to release bradykinin, which is composed of only nine amino acids [35]. Lower HMWK and higher kinin levels are associated with age-related diseases, including Alzheimer's Disease (AD) and impaired cognitive function [36][37][38][39]. Finally, activated F11 is a component of both thrombin generation and the kallikrein-kinin system [40].…”

Section: Discussionmentioning

confidence: 99%

Cross-platform proteomics signatures of extreme old age

Reed,

Chandler,

Lopez

et al. 2024

Preprint

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In previous work we used a Somalogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals.

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Section: Discussionmentioning

confidence: 99%

Cross-platform proteomics signatures of extreme old age

Reed,

Chandler,

Lopez

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…For instance, in cardiovascular diseases, vascular dysfunction plays a pivotal role in the development of conditions like atherosclerosis, hypertension, and heart failure [23][24][25]. In neurodegenerative diseases, such as Alzheimer's disease, vascular dysfunction disrupts the delicate balance of nutrient supply and waste removal, including the clearance of amyloid β (Aβ) in the brain [26,27]. This acceleration of neurodegeneration contributes to cognitive decline.…”

Section: Vascular Dysfunction In Degenerative Diseasesmentioning

confidence: 99%

“…vi. Alzheimer's Disease: In AD, cerebral vessel integrity is compromised due to the deposition of Aβ, resulting in cerebral amyloid angiopathy [27,42]. These abnormal protein deposits can affect blood vessels, reducing cerebral blood flow.…”

Section: The Impact Of Degenerative Diseases On Vascular Dysfunctionmentioning

confidence: 99%

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications

Sheikh,

Yano,

Tabassum

et al. 2024

IJMS

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Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer’s and Parkinson’s, emphasizing the critical role of cerebral blood flow regulation and the blood–brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health.

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“…Chronic cerebral hypoperfusion, resulting from vascular pathology, can exacerbate β-amyloid deposition and tau pathology and increase the risk of cognitive impairment. 24,25 While most cases of AD are sporadic, a small percentage are inherited in an autosomal dominant fashion, known as familial Alzheimer's disease (FAD). 26 Mutations in genes such as amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are associated with early-onset FAD, leading to increased production or altered processing of β-amyloid.…”

Section: Pathogenesismentioning

confidence: 99%

Alzheimer's Disease: Exploring the Landscape of Cognitive Decline

Tenchov,

Sasso,

Zhou

2024

Preprint

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. The pathology of AD is marked by the accumulation of amyloid-beta plaques and tau protein tangles in brain, along with neuroinflammation and synaptic dysfunction. Genetic factors, such as mutations in APP, PSEN1, and PSEN2 genes, as well as APOE ε4 allele, contribute to increased risk of acquiring AD. Currently available treatments provide symptomatic relief but do not halt disease progression. Research efforts are focused on developing disease-modifying therapies that target the underlying pathological mechanisms of AD. Advances in identification and validation of reliable biomarkers for AD hold great promise for enhancing early diagnosis, monitoring disease progression, and assessing treatment response in clinical practice, in effort to alleviate the burden of this devastating disease. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in Alzheimer’s disease. We examine the publication landscape in effort to provide insights into current knowledge advances and developments. We also review the most discussed and emerging concepts and assess the strategies to combat the disease. We explore the genetic risk factors, pharmacological targets, and comorbid diseases. Finally, we inspect clinical applications of products against AD with their development pipelines and efforts for drug repurposing. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding AD, to outline challenges, and evaluate growth opportunities to further efforts in combating the disease.

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Vascular Dysfunction in Alzheimer’s Disease: Alterations in the Plasma Contact and Fibrinolytic Systems

Cited by 10 publications

References 127 publications

Cross-platform proteomics signatures of extreme old age

Cross-platform proteomics signatures of extreme old age

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications

Alzheimer's Disease: Exploring the Landscape of Cognitive Decline

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