Overlapping Protein Accumulation Profiles of CADASIL and CAA

Young, Kelly Z.; Xu, Gang; Keep, Simon G.; Borjigin, Jimo; Wang, Michael M.

doi:10.1016/j.ajpath.2020.11.015

Cited by 15 publications

(7 citation statements)

References 115 publications

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“…The gradual imbalance of the various proteostasis machineries, frequently in combination with disorders of protein processing and aggregation through mutated, misfolding, hyperphosphorylated proteins, is increasingly recognized as important pathological mechanisms of the aging brain, especially in neurodegenerative diseases. Impaired proteostasis and protein aggregation might also contribute to CSVD, most prominently cerebral amyloid angiopathy (CAA) and cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [ 83 , 84 ].…”

Section: The Underlying Role Of the Glymphatic And Meningeal Lymphati...mentioning

confidence: 99%

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease

et al. 2022

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There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main contributor to VCI. Several potential physiopathologic mechanisms have been proven to be involved in the process of CSVD, such as blood-brain barrier damage, small vessels stiffening, venous collagenosis, cerebral blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin damage, and subsequent neurodegeneration. However, there still is a limited overall understanding of the sequence and the relative importance of these mechanisms. The glymphatic system (GS) and meningeal lymphatic vessels (mLVs) are the analogs of the lymphatic system in the central nervous system (CNS). As such, these systems play critical roles in regulating cerebrospinal fluid (CSF) and interstitial fluid (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence has suggested that the glymphatic and meningeal lymphatic vessels played vital roles in animal models of CSVD and patients with CSVD. Given the complexity of CSVD, it was significant to understand the underlying interaction between glymphatic and meningeal lymphatic transport with CSVD. Here, we provide a novel framework based on new advances in main four aspects, including vascular risk factors, potential mechanisms, clinical subtypes, and cognition, which aims to explain how the glymphatic system and meningeal lymphatic vessels contribute to the progression of CSVD and proposes a comprehensive insight into the novel therapeutic strategy of CSVD.

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Section: The Underlying Role Of the Glymphatic And Meningeal Lymphati...mentioning

confidence: 99%

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease

et al. 2022

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“…89 Impaired clearance may be a shared mechanism in CADASIL and cerebral amyloid angiopathy-Alzheimer disease, which feature a modest number of overlapping proteins. 24,90 An overlap between CADASIL vessel proteins and targets of the CARASIL factor HTRA1, a protease, implicates convergent pathways of impaired protein clearance in CADASIL and CARASIL. 91 In addition, decreased baseline relaxation of vascular smooth muscle cells due to abnormalities in sGC/cGMP signaling 92 and inadequate H 2 O 2 production compound defects in vessel reactivity in animal models.…”

Section: Pathways To Disease-modifying Therapiesmentioning

confidence: 99%

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association

Meschia,

Worrall,

Elahi

et al. 2023

Stroke

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Lacunar infarcts and vascular dementia are important phenotypic characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the most common inherited cerebral small vessel disease. Individuals with the disease show variability in the nature and onset of symptoms and rates of progression, which are only partially explained by differences in pathogenic mutations in the NOTCH3 gene. Recognizing the disease early in its course and securing a molecular diagnosis are important clinical goals, despite the lack of proven disease-modifying treatments. The purposes of this scientific statement are to review the clinical, genetic, and imaging aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, contrasting it with other inherited small vessel diseases, and to provide key prevention, management, and therapeutic considerations with the intent of reducing practice variability and encouraging production of high-quality evidence to support future treatment recommendations.

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“…Some disease boundaries in small blood vessel disease may be only artificial, as suggested by findings discussed by Wang et al supporting major commonalities between CADASIL and cerebral amyloid arteriopathy. 5 These conditions were thought of as completely different from each other, at least mechanistically. Consistent with the subtheme of breaking artificial disease boundaries, Sepulveda-Falla and Kalaria's contribution discusses existing evidence for small blood vessel disease in sporadic and familial AD, proposing the need of incorporating relevant vascular biomarkers in the biological definition of AD.…”

Section: Q8mentioning

confidence: 99%

Safe and Effective Disease-Modifying Therapies for Small Blood Vessel Disease in the Brain

Arboleda‐Velásquez

2021

The American Journal of Pathology

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Disclosures: J.F.A-V is listed as an inventor in patent applications for biomarkers and treatments addressing cerebral small vessel disease.J.F.A-V is the Special Editor of the Small Blood Vessel Disease in the Brain Theme Issue.This Editorial introduces this month's special Small Blood Vessel Disease in the Brain Theme Issue, a series of reviews on small blood vessel disease in the brain addressing current knowledge, new mechanisms, biomarkers, and therapeutic approaches.

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Overlapping Protein Accumulation Profiles of CADASIL and CAA

Cited by 15 publications

References 115 publications

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease

The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association

Safe and Effective Disease-Modifying Therapies for Small Blood Vessel Disease in the Brain

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