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

Abstract

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.

Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer’s Disease

“…Our findings were consistent with other studies that also found lower platelet A␤PP ratios in AD patients compared to HCs [31,32]. It is well known that platelets are the major source of peripheral A␤ in human blood [20]. Recent studies showed that platelets could disrupt the permeability of the BBB [21,22] and transfer A␤ from blood vessels into the central nervous system [33].…”

Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer’s Disease

“…Our findings were consistent with other studies that also found lower platelet A␤PP ratios in AD patients compared to HCs [31,32]. It is well known that platelets are the major source of peripheral A␤ in human blood [20]. Recent studies showed that platelets could disrupt the permeability of the BBB [21,22] and transfer A␤ from blood vessels into the central nervous system [33].…”

Targeting Gliomas with Beta-Amyloid-Specific Dyes: A Novel Approach for In Vivo Staining and Potential Therapeutic Applications

“…We interpret this shift as evidence that BBG first binds to soluble oligomeric Aβ or other filamentous peptides in the peritumoral space—material that is subsequently washed away during the H&E staining process—before concentrating within tumor cells. Given that extracellular Aβ oligomers form soluble filamentous plaques in rodents [ 30 ], our data may represent the first detection of such soluble Aβ oligomers in the glioma microenvironment, as previously hypothesized [ 31 , 32 ]. In addition to in vivo administration, we also examined whether BBG can directly stain glioma tissue in the absence of vascular delivery.…”

Gamma-Synuclein Dysfunction Causes Autoantibody Formation in Glaucoma Patients and Dysregulation of Intraocular Pressure in Mice

“…α2-MG is a protein of acute phase inflammation, an inhibitor of a wide range of proteolytic enzymes, and a regulator of the function of many cytokines and growth factors. As an extracellular chaperone, α2-MG prevents the formation of misfolded proteins and their conglomerates, including amyloid-β, which accumulates in the retina in glaucoma [45][46][47][48][49]. We noticed a significant increase in the concentration of total protein in the tear fluid of γ-KO mice.…”

Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer’s Disease

“…Our findings were consistent with other studies that also found lower platelet A␤PP ratios in AD patients compared to HCs [31,32]. It is well known that platelets are the major source of peripheral A␤ in human blood [20]. Recent studies showed that platelets could disrupt the permeability of the BBB [21,22] and transfer A␤ from blood vessels into the central nervous system [33].…”

Targeting Gliomas with Beta-Amyloid-Specific Dyes: A Novel Approach for In Vivo Staining and Potential Therapeutic Applications

“…We interpret this shift as evidence that BBG first binds to soluble oligomeric Aβ or other filamentous peptides in the peritumoral space—material that is subsequently washed away during the H&E staining process—before concentrating within tumor cells. Given that extracellular Aβ oligomers form soluble filamentous plaques in rodents [ 30 ], our data may represent the first detection of such soluble Aβ oligomers in the glioma microenvironment, as previously hypothesized [ 31 , 32 ]. In addition to in vivo administration, we also examined whether BBG can directly stain glioma tissue in the absence of vascular delivery.…”

Gamma-Synuclein Dysfunction Causes Autoantibody Formation in Glaucoma Patients and Dysregulation of Intraocular Pressure in Mice

“…α2-MG is a protein of acute phase inflammation, an inhibitor of a wide range of proteolytic enzymes, and a regulator of the function of many cytokines and growth factors. As an extracellular chaperone, α2-MG prevents the formation of misfolded proteins and their conglomerates, including amyloid-β, which accumulates in the retina in glaucoma [45][46][47][48][49]. We noticed a significant increase in the concentration of total protein in the tear fluid of γ-KO mice.…”

Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer’s Disease

“…Our findings were consistent with other studies that also found lower platelet A␤PP ratios in AD patients compared to HCs [31,32]. It is well known that platelets are the major source of peripheral A␤ in human blood [20]. Recent studies showed that platelets could disrupt the permeability of the BBB [21,22] and transfer A␤ from blood vessels into the central nervous system [33].…”

Targeting Gliomas with Beta-Amyloid-Specific Dyes: A Novel Approach for In Vivo Staining and Potential Therapeutic Applications

“…We interpret this shift as evidence that BBG first binds to soluble oligomeric Aβ or other filamentous peptides in the peritumoral space—material that is subsequently washed away during the H&E staining process—before concentrating within tumor cells. Given that extracellular Aβ oligomers form soluble filamentous plaques in rodents [ 30 ], our data may represent the first detection of such soluble Aβ oligomers in the glioma microenvironment, as previously hypothesized [ 31 , 32 ]. In addition to in vivo administration, we also examined whether BBG can directly stain glioma tissue in the absence of vascular delivery.…”

Gamma-Synuclein Dysfunction Causes Autoantibody Formation in Glaucoma Patients and Dysregulation of Intraocular Pressure in Mice

“…α2-MG is a protein of acute phase inflammation, an inhibitor of a wide range of proteolytic enzymes, and a regulator of the function of many cytokines and growth factors. As an extracellular chaperone, α2-MG prevents the formation of misfolded proteins and their conglomerates, including amyloid-β, which accumulates in the retina in glaucoma [45][46][47][48][49]. We noticed a significant increase in the concentration of total protein in the tear fluid of γ-KO mice.…”