Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease

Ahn, Hyung Jin; Chen, Zu Lin; Zamolodchikov, Daria; Norris, Erin H.; Strickland, Sidney

doi:10.1097/moh.0000000000000368

Cited by 44 publications

(31 citation statements)

References 51 publications

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“…Recent studies (e.g. Ahn et al ., , , ; Cortes‐Canteli et al ., , ; Cortes‐Canteli & Strickland, ; Zamolodchikov et al ., ; Zamolodchikov & Strickland, ) have highlighted its interaction with Aβ peptides in Alzheimer's disease. Here, it is important to recognise that the faster kinetics of a given amyloidogenic process (such as fibrin formation) might accelerate the kinetics of a different amyloid with which it happens to interact, and that this could have important implications for the initiation of overt disease.…”

Section: Step 6: Induction Of Fibrin Amyloid Formation By ‘Iron’ Lpsmentioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.

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Section: Step 6: Induction Of Fibrin Amyloid Formation By ‘Iron’ Lpsmentioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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“…Notably, brinogen and its cleavage products are known to contribute to in ammation in the CNS by a variety of mechanisms including microglial activation [77,78], neuronal damage [79], interactions with beta-amyloid [80], and disruption of the blood-brain barrier [81]. In fact, alterations in CNS brinogen biology have been implicated in the pathogenesis of neurological, neurocognitive, and psychiatric disorders including multiple sclerosis [82], traumatic brain injury [83], Alzheimer's disease [78,84], and depression [85]. Likewise, coagulation factor V, a central mediator of hemostasis, has been previously linked to delirium pathogenesis [33].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

VanDusen

et al. 2020

Preprint

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Background: Postoperative cognitive dysfunction (POCD) is a syndrome of cognitive deficits that occurs in 10-40% of patients age > 60 within 1-12 months after surgery, hypothesized to be caused in part by neuroinflammation. However, the specific neuroinflammatory pathways involved remain unclear. Unbiased mass spectrometry-based proteomic analyses have been used to identify neuro-inflammatory pathways in multiple neurologic diseases and syndromes but have not yet been used in the POCD field. Thus, we used unbiased mass spectrometry-based proteomics to compare cerebrospinal fluid (CSF) samples from patients with and without POCD to identify potential neuroinflammatory pathways for further investigation in future studies. Methods: We performed unbiased LC-MS/MS proteomics on immunodepleted CSF samples obtained before, 24 hours, and 6 weeks after major non-cardiac surgery in older adults who developed (n=8) or did not develop POCD (n=6). General linear mixed models were used to identify peptides and proteins with intensity differences between groups or over time by groups. Kyoto Encyclopedia of Genes and Genomes analysis was used to identify pathways containing proteins/peptides with q values < 0.25 in the mixed model. Results: Mass spectrometry quantified 8258 peptides from 1222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between groups (POCD vs non-POCD) at q < 0.05, including several from proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these patient groups. Of these 283 peptides with trend-level significance, pathway analysis revealed that 50 of them were from 17 proteins that mapped to the complement and coagulation pathways (q=2.44*10-13).Conclusions: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify peptides, proteins, and pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

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“…In our study, we found an increase in plasminogen, brinogen and kininogen. In AD, plasminogen was found to colocalize with Aβ plaques [37], while brinogen was capable of enhancing Aβ aggregation and brillization, causing impairment in AD [48,49]. Patients with higher levels of plasma brinogen and plasminogen modulating neuroin ammation had worsening cognitive decline and Aβ deposition [37,50,51].…”

Section: Discussionmentioning

confidence: 99%

The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

Phochantachinda¹,

Chantong²,

Reamtong³

et al. 2020

Preprint

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Background: Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification.Results: Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 45 and 52 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p = 0.125, R2 = 0.27).Conclusions: Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis.

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Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease

Cited by 44 publications

References 51 publications

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

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Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease

Cited by 44 publications

References 51 publications

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

The Plasma Amyloid Beta 42&nbsp;(Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

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The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand