Platelets Are the Primary Source of Amyloid β-Peptide in Human Blood

Chen, Ming; Inestrosa, N. C.; Ross, George; Fernández, Hugo L.

doi:10.1006/bbrc.1995.2103

Cited by 295 publications

(189 citation statements)

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“…Ex vivo we found that serum had higher levels of APP and A␤ than plasma. Our study supports the notion that platelets are a source of both peptides in the circulation (5,8,11). However, the pharmacological suppression of platelet COX activity by aspirin, as assessed by the dramatic reduction of serum TxB 2 , did not interfere with platelet capacity to release APP or A␤, confirming our in vitro observations.…”

Section: Discussionsupporting

confidence: 90%

Amyloid Precursor Protein and Amyloid β Peptide in Human Platelets

Skovronsky¹,

Lee

Praticò

2001

Journal of Biological Chemistry

108

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The main component of Alzheimer's disease (AD) senile plaques is amyloid-␤ peptide (A␤), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and A␤ and may contribute to the perivascular amyloid deposition seen in AD. However, no data are available concerning the biochemical mechanism(s) involved in their formation and release by these cells. We found that human platelets released APP and A␤ following activation with collagen or arachidonic acid. Inhibition of platelet cyclooxygenase (COX) reduced APP but not A␤ release following those stimuli. In contrast, activation of platelets by thrombin and calcium ionophore caused release of both APP and A␤ in a COX-independent fashion. Ex vivo studies showed that, despite suppression of COX activity, administration of aspirin did not modify A␤ or APP levels in serum or plasma, suggesting that this enzyme plays only a minor role in vivo. We examined the regulation of APP cleavage and release from activated platelets and found that cleavage requires protein kinase C (PKC) activity and is regulated by the intracellular second messengers phosphatidylinositol 2-phosphate and Ca 2؉. Our data provide the first evidence that in human platelets COX is a minor component of APP secretion whereas PKC plays a major role in the secretory cleavage of APP. By contrast, A␤ release may represent secretion of preformed peptide and is totally independent of both COX and PKC activity.

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Section: Discussionsupporting

confidence: 90%

Amyloid Precursor Protein and Amyloid β Peptide in Human Platelets

Skovronsky¹,

Lee

Praticò

2001

Journal of Biological Chemistry

108

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“…15 Increases in the Aβ40/Aβ42 ratio may promote the deposition of Aβ from the parenchyma to the blood vessels. However, Aβ peptides in the blood may be synthesized outside the brain 9 mainly by platelets, 16 but also by liver and kidney. Aβ can be found in the blood and cerebrospinal fluid of healthy individuals, and both the cerebral and peripheral pools of Aβ can cross the BBB in both directions.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Plasma β-Amyloid Levels in Patients With Acute Intracerebral Hemorrhage

Martí‐Fàbregas

Delgado‐Mederos

Marín

et al. 2014

Stroke

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Background and Purpose— It has been proposed that the deposition of the β-amyloid peptide (Aβ) in the brain parenchyma and brain blood vessels has deleterious effects. We tested the hypothesis that the levels of plasma Aβ are related to the outcome in patients with intracerebral hemorrhage. Methods— In a multicenter study, we prospectively included patients with spontaneous intracerebral hemorrhage within the first 24 hours after onset. At admission, we measured plasma Aβ40 and Aβ42 levels using ELISA techniques. Also, we recorded age, sex, vascular risk factors, National Institutes of Health Stroke Scale score, presence of intraventricular hemorrhage, localization, cause, and volume of the hematoma. We obtained the modified Rankin scale and defined a unfavorable outcome as modified Rankin scale >2 at 3 months. Bivariate and multivariate regression analyses were performed. Results— We studied 160 patients (mean age, 73.8±11.3 years; 59.4% of them were men). A favorable outcome was observed in 64 (40%) of the patients. In the bivariate analyses, unfavorable outcome was associated with high age, female sex, diabetes mellitus, presence of intraventricular hemorrhage, high blood glucose, high National Institutes of Health Stroke Scale score, high volume, and high plasma levels of Aβ42 and Aβ40. The multivariate analysis showed that increased age (odds ratio, 1.07; 95% confidence interval, 1.035–1.21; P <0.0001), high admission National Institutes of Health Stroke Scale score (odds ratio, 1.29, 95% confidence interval, 1.17–1.42; P <0.0001), presence of diabetes mellitus (odds ratio, 4.15; 95% confidence interval, 1.21–14.1; P =0.02), and Aβ42 levels >9.7 pg/mL (odds ratio, 4.11; 95% confidence interval, 1.65–10.1; P =0.02) were independently associated with an increased likelihood of an unfavorable outcome. Conclusions— High levels of plasma Aβ42 in patients with acute intracerebral hemorrhage are associated with a poor functional prognosis.

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“…Platelets are responsible for up to 90% of the anti-AI] immunoreactivity in whole blood [23], representing a probable source of sA~. After the discovery by linkage analysis of the relationship between the majority of the cases of early-onset FAD and the PSI gene [6] we decided to investigate whether platelets also express PSI protein.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Vidal¹,

Ghiso²,

Wısnıewskı³

et al. 1996

FEBS Letters

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The presenilin 1 (PSI) gene located on chromosome 14 has been linked with the majority of early-onset FAD. The normal biological role of PS1 as well as the mechanism by which mutations in PSI cause FAD remains unknown. PSI expression in platelets and the Dami megakaryocytic cell line was examined by Western blot analysis and RT-PCR. Using an anti-Nterminus PS1 antibody we detected PSI immunoreactive bands of 44, 32 and 27 kDa in both cell types. After RT-PCR we observed that platelets and megakaryocytes carry at least four different PSI transcripts. One of them is a novel PSI splice variant that lacks the coding sequence for exon 10 resulting in a shorter 409 amino acid protein.

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Platelets Are the Primary Source of Amyloid β-Peptide in Human Blood

Cited by 295 publications

References 0 publications

Amyloid Precursor Protein and Amyloid β Peptide in Human Platelets

Amyloid Precursor Protein and Amyloid β Peptide in Human Platelets

Prognostic Value of Plasma β-Amyloid Levels in Patients With Acute Intracerebral Hemorrhage

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

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