Amyloid Beta Peptide Is Released during Thrombosis in the Skin

Kucheryavykh, Lilia; Kucheryavykh, Yuriy V.; Washington, A. Valance; Inyushin, Mikhail

doi:10.3390/ijms19061705

Cited by 14 publications

(23 citation statements)

References 84 publications

(105 reference statements)

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“…It was proposed that Aβ accumulation in astrocytes and on blood vessel walls is related to ischemia in these processes, while both brain cells ( 30 ) and platelets ( 35 – 38 ) can be the source of Aβ. Using immunocytochemistry, we detected a massive release of Aβ peptides in and around blood vessels in the brain and skin after experimental thrombosis, and we determined the source of these peptides to be platelets ( 39 , 40 ). Interestingly, according to evidence in the literature, murine Aβ deposits are transient after traumatic brain injury, while in humans, they are relatively stable.…”

Section: Aβ Peptide Accumulation Is Associated With a Variety Of Disementioning

confidence: 99%

“…Here it should be remarked that, while it is known that Aβ peptides in humans can be of different lengths, with different properties, reported measurements of the Aβ40/Aβ42 ratio in many pathologies (except AD) are unfortunately rare, and we will not discuss this issue here. Moreover, the buildup of extracellular plaques due to Aβ aggregation occurs in brain tissue, in the vicinity of skin blood vessels, or in peripheral blood vessels in internal organs ( 40 , 66 ). Most likely, it is related to the difference in blood vessel wall structure in these areas and in other parts of the body.…”

Section: Aβ Peptide Accumulation Is Associated With a Variety Of Disementioning

confidence: 99%

“…Other defensins can form large, weakly anion-selective ion channels, and this channel-forming ability contributes to their antimicrobial properties ( 82 ). Equally, we have shown that a synthetic Aβ peptide perforates the external membrane of yeast ( 40 ), and it is known that natural peptide antibiotics with channel-forming activity kill target cells, including fungi, by this same mechanism ( 83 , 84 ). It was shown earlier that soluble Aβ peptide oligomers at low concentrations perforate cell membranes by forming tetrameric/octameric channels penetrable by K + ions, while at higher concentrations they form large, non-selective pores ( 85 – 89 ).…”

Section: Aβ Is An Innate Immunity Weapon Released By Plateletsmentioning

confidence: 99%

“…Aβ immunostaining was intense inside and near blood vessels in the thrombotic zone, with the maximum intensity near the vessel walls ( 39 ). Similarly, Aβ generated from precursors released from platelets might be the source of its accumulation in mouse skin, as it was found to be concentrated around blood vessels after experimental thrombosis ( 40 ). A similar accumulation of Aβ around blood vessels in the skin of AD patients and generally in older patients was described many years ago ( 66 , 139 ).…”

Section: Aβ Is a Vital Defense Protein With Multiple Rolesmentioning

confidence: 99%

“…When directly activated by viral and bacterial antigens, platelets release microbicidal peptides ( 16 , 154 – 162 ). We have shown that Aβ peptides perforate yeast cell membranes while not affecting somatic cell membranes at the same concentration ( 40 ). Apart from Aβ peptide, there are other antibacterial peptides released by platelets.…”

Section: Aβ Is a Vital Defense Protein With Multiple Rolesmentioning

confidence: 99%

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On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

et al. 2020

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As do many other immunity-related blood cells, platelets release antimicrobial peptides that kill bacteria, fungi, and even certain viruses. Here we review the literature suggesting that there is a similarity between the antimicrobials released by other blood cells and the amyloid-related Aβ peptide released by platelets. Analyzing the literature, we also propose that platelet-generated Aβ amyloidosis may be more common than currently recognized. This systemic Aβ from a platelet source may participate in various forms of amyloidosis in pathologies ranging from brain cancer, glaucoma, skin Aβ accumulation, and preeclampsia to Alzheimer’s disease and late-stage Parkinson’s disease. We also discuss the advantages and disadvantages of specific animal models for studying platelet-related Aβ. This field is undergoing rapid change, as it evaluates competing ideas in the light of new experimental observations. We summarized both in order to clarify the role of platelet-generated Aβ peptides in amyloidosis-related health disorders, which may be helpful to researchers interested in this growing area of investigation.

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Section: Aβ Peptide Accumulation Is Associated With a Variety Of Disementioning

confidence: 99%

Section: Aβ Peptide Accumulation Is Associated With a Variety Of Disementioning

confidence: 99%

Section: Aβ Is An Innate Immunity Weapon Released By Plateletsmentioning

confidence: 99%

Section: Aβ Is a Vital Defense Protein With Multiple Rolesmentioning

confidence: 99%

Section: Aβ Is a Vital Defense Protein With Multiple Rolesmentioning

confidence: 99%

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On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

et al. 2020

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Senile plaques in Alzheimer's disease arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture

et al. 2022

FEBS Letters

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Senile plaques are a pathological hallmark of Alzheimer's disease (AD), yet the mechanism underlying their generation remains unknown. Beta‐amyloid peptide (Aβ) is a major component of senile plaques. We analysed AD brain tissues with histochemistry, immunohistochemistry and fluorescence imaging to examine the neural, vascular or blood Aβ contribution to senile plaque development. We found little neural marker co‐expression with plaque Aβ, while co‐expression of blood markers, such as Haemin and ApoE, was abundant. The plaque cores were structured with vascular and glial proteins outside and blood metabolites inside, co‐localizing with a characteristic of Hoechst staining‐independent blue autofluorescence. Erythrocyte‐interacting Aβ is linked to coagulation, elevated calcium and blue autofluorescence, and it is associated with intravascular haemolysis, atherosclerosis, cerebral amyloid angiopathy, microaneurysm, and often with Cathepsin D co‐expression. We identified microaneurysms as major sites of amyloid formation. Our data suggest that senile plaques arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture.

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Accumulation of amyloid beta (Aβ) and amyloid precursor protein (APP) in tumors formed by a mouse xenograft model of inflammatory breast cancer

et al. 2021

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Accumulation of amyloid in breast cancer is a well-known phenomenon, but only immunoglobulin light-chain amyloidosis (AL) or transthyretin (TTR) amyloid had been detected in human breast tumor samples previously. We recently reported that another amyloidogenic peptide, amyloid beta (Ab), is present in an aggregated form in animal and human highgrade gliomas and suggested that it originates systemically from the blood, possibly generated by platelets. To study whether breast cancers are also associated with these Ab peptides and in what form, we used a nude mouse model inoculated with triple-negative inflammatory breast cancer cell (SUM-149) xenografts, which develop noticeable tumors. Immunostaining with two types of specific antibodies for Ab identified the clear presence of Ab peptides associated with (a) carcinoma cells and (b) extracellular aggregated amyloid (also revealed by Congo red and thioflavin S staining). Ab peptides, in both cells and in aggregated amyloid, were distributed in clear gradients, with maximum levels near blood vessels. We detected significant presence of amyloid precursor protein (APP) in the walls of blood vessels of tumor samples, as well as in carcinoma cells. Finally, we used ELISA to confirm the presence of elevated levels of mouse-generated Ab40 in tumors. We conclude that Ab in inflammatory breast cancer tumors, at least in a mouse model, is always present and is concentrated near blood vessels. We also discuss here the possible pathways of Ab accumulation in tumors and whether this phenomenon could represent the specific signature of highgrade cancers.Inflammatory breast cancer (IBC) is one of the most aggressive types of this disease; it is highly metastatic and usually fatal (as it is commonly diagnosed at T4, according to the tumor-nodes-metastasis classification of cancers (TNM) classification). Various IBC carcinoma cell subtypes exist, with the triple-negative subtype the most frequently diagnosed. These tumors lack receptors for estrogen, progesterone, or human epidermal growth factor receptor 2 (proto-oncogene) (HER2/neu), and thus, IBC is often treated with chemotherapy, radiation, or Abbreviations AD, Alzheimer's disease; AL, light-chain amyloidosis; APP, amyloid precursor protein; Ab, amyloid beta; DAPI-4 0 , 6-diamidino-2-phenylindole; ELISA, enzyme-linked immunosorbent assay; HER2/neu, human epidermal growth factor receptor 2 (proto-oncogene); IBC, inflammatory breast cancer; SUM-149-IBC cell line; MALT, mucosa-associated lymphoid tissue; MAPK, mitogen-activated protein kinases; PDGF, plateletderived growth factor; SCID, severe combined immunodeficient (mice strain); TNM, tumor-nodes-metastasis classification of cancers; TTR, transthyretin.

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Amyloid Beta Peptide Is Released during Thrombosis in the Skin

Cited by 14 publications

References 84 publications

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

Senile plaques in Alzheimer's disease arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture

Accumulation of amyloid beta (Aβ) and amyloid precursor protein (APP) in tumors formed by a mouse xenograft model of inflammatory breast cancer

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