Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy

Inoue, Yasuteru; Ueda, Mitsuharu; Tasaki, Masayoshi; Takeshima, Akari; Nagatoshi, Akihito; Masuda, Teruaki; Misumi, Yohei; Kosaka, Takayuki; Nomura, Toshiya; Mizukami, Mayumi; Matsumoto, Sayaka; Yamashita, Taro; Takahashi, Hitoshi; Kakita, Akiyoshi; Ando, Yumiko

doi:10.1007/s00401-017-1720-z

Cited by 24 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inoue and coworkers performed proteomics on eight cases of severe CAA, 12 cases of mild CAA and 10 controls (Inoue et al . ), 60% of the CAA cases and 15% of control cases had Braak stages of three and above. It is stated that six proteins were significantly higher expressed in severe CAA, i.e., Aβ, APOE , GFAP , ENO 1/3 , and SRPX1 .…”

Section: Proteome From Ad Patients With Cerebral Amyloid Angiopathymentioning

confidence: 88%

Proteomics of neurodegenerative diseases: analysis of human post‐mortem brain

Ganz

Smit

2018

Journal of Neurochemistry

View full text Add to dashboard Cite

Dementias are prevalent brain disorders in the aged population. Dementias pose major socio‐medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These studies confirmed known cellular changes, and in addition identified novel proteins that may underlie distinct aspects of the diseases. https://onlinelibrary.wiley.com/page/journal/14714159/homepage/virtual_issues.htm.

show abstract

Section: Proteome From Ad Patients With Cerebral Amyloid Angiopathymentioning

confidence: 88%

Proteomics of neurodegenerative diseases: analysis of human post‐mortem brain

Ganz

Smit

2018

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Two recent proteomics studies focussed on CAA analysing leptomeningeal vessels [ 27 ] and leptomeningeal vessel combined with neocortical arterioles [ 28 ]. Some similarities were found with these studies, such as the increase in CLU and APOE.…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer’s disease

Hondius

Eigenhuis

Morrema

et al. 2018

acta neuropathol commun

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) deposits as plaques in the parenchyma and in the walls of cortical and leptomeningeal blood vessels of the brain called cerebral amyloid angiopathy (CAA). It is suggested that CAA type-1, which refers to amyloid deposition in both capillaries and larger vessels, adds to the symptomatic manifestation of AD and correlates with disease severity. Currently, CAA cannot be diagnosed pre-mortem and disease mechanisms involved in CAA are elusive. To obtain insight in the disease mechanism of CAA and to identify marker proteins specifically associated with CAA we performed a laser dissection microscopy assisted mass spectrometry analysis of post-mortem human brain tissue of (I) AD cases with only amyloid deposits in the brain parenchyma and no vascular related amyloid, (II) AD cases with severe CAA type-1 and no or low numbers of parenchymal amyloid deposits and (III) cognitively healthy controls without amyloid deposits. By contrasting the quantitative proteomics data between the three groups, 29 potential CAA-selective proteins were identified. A selection of these proteins was analysed by immunoblotting and immunohistochemistry to confirm regulation and to determine protein localization and their relation to brain pathology. In addition, specificity of these markers in relation to other small vessel diseases including prion CAA, CADASIL, CARASAL and hypertension related small vessel disease was assessed using immunohistochemistry.Increased levels of clusterin (CLU), apolipoprotein E (APOE) and serum amyloid P-component (APCS) were observed in AD cases with CAA. In addition, we identified norrin (NDP) and collagen alpha-2(VI) (COL6A2) as highly selective markers that are clearly present in CAA yet virtually absent in relation to parenchymal amyloid plaque pathology. NDP showed the highest specificity to CAA when compared to other small vessel diseases. The specific changes in the proteome of CAA provide new insight in the pathogenesis and yields valuable selective biomarkers for the diagnosis of CAA.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0540-2) contains supplementary material, which is available to authorized users.

show abstract

“…Proteomic analysis of vascular amyloid has confirmed the presence and abundance of apolipoprotein E or apolipoprotein J in leptomeningeal and cortical vessels from the brains of patients with CAA 150,181,182 . Other potentially important proteins that were identified in these studies as being associated with vascular amyloid but not with neuritic plaques include metalloproteinase inhibitor 3 181 , norrin, collagen α-2 (VI) chain 182 and sushi repeatcontaining protein 1 (SRPX1) 183 . Some of these co-localized proteins suggest mechanisms that contribute to vessel injury, such as the ability of SRPX1 to increase Aβ 40 -induced caspase activity 183 , but the pathogenic roles of these proteins, if they have any, are unknown.…”

Section: Aβ Peptide Length-althoughmentioning

confidence: 99%

“…Other potentially important proteins that were identified in these studies as being associated with vascular amyloid but not with neuritic plaques include metalloproteinase inhibitor 3 181 , norrin, collagen α-2 (VI) chain 182 and sushi repeatcontaining protein 1 (SRPX1) 183 . Some of these co-localized proteins suggest mechanisms that contribute to vessel injury, such as the ability of SRPX1 to increase Aβ 40 -induced caspase activity 183 , but the pathogenic roles of these proteins, if they have any, are unknown. Deposition of fibrinogen -a precursor of fibrin and a principal contributor to haemostasis -has also been detected in CAA-positive vessels in AD 184 , and the extent of deposition was greatest in people who were homozygotic for APOE*ε4 (ref.…”

Section: Aβ Peptide Length-althoughmentioning

confidence: 99%

Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways

et al. 2019

View full text Add to dashboard Cite

The shared role of amyloid-β (Aβ) deposition in cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) is arguably the clearest instance of cross-talk between neurodegenerative and cerebrovascular processes. The pathogenic pathways of CAA and AD intersect at the levels of Aβ generation, its circulation within the interstitial fluid and perivascular drainage pathways and its brain clearance, but diverge in their mechanisms of brain injury and disease presentation. Here, we review the evidence for and pathogenic implications of interactions between CAA and AD. Both pathologies seem to be driven by impaired Aβ clearance, creating conditions for a selfreinforcing cycle of increased vascular Aβ, reduced perivascular clearance and further CAA and AD progression. Despite the close relationship between vascular and plaque Aβ deposition, several factors favour one or the other, such as the carboxy-terminal site of the peptide and specific co-deposited proteins. Amyloid-related imaging abnormalities that have been seen in trials of anti-Aβ immunotherapy are another probable intersection between CAA and AD, representing overload of perivascular clearance pathways and the effects of removing Aβ from CAA-positive vessels. The intersections between CAA and AD point to a crucial role for improving vascular function in the treatment of both diseases and indicate the next steps necessary for identifying therapies.

show abstract

Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy

Cited by 24 publications

References 30 publications

Proteomics of neurodegenerative diseases: analysis of human post‐mortem brain

Proteomics of neurodegenerative diseases: analysis of human post‐mortem brain

Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer’s disease

Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways

Contact Info

Product

Resources

About