Activated Alzheimer Disease Platelets Retain More Beta Amyloid Precursor Protein

Davies, Theresa A.; Long, Heidi J.; Sgro, Kimberly R.; Rathbun, Wayne; McMenamin, Mary E.; Seetoo, Kurt F.; Tibbles, Heather E.; Billingslea, Andrea M.; Fine, Richard E.; Fishman, Jordan B.; Levesque, C.A; Smith, Sally J.; Wells, John M.; Simons, Elizabeth R.

doi:10.1016/s0197-4580(97)00013-4

Cited by 52 publications

(28 citation statements)

References 21 publications

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“…However, we found that convulxin plus thrombin stimulation was required to retain APP on platelets while Davies et al [9] observed the same APP retention with just thrombin stimulation. Thrombin alone at high concentrations can produce coated-platelets [5], although the levels utilized by Davies et al [8] do not generally generate coatedplatelets [5]. Furthermore, we observed an increased propensity to form coated-platelets among the least affected AD patients while Davies et al [9] observed a change only among the most severely affected AD patients.…”

Section: Discussioncontrasting

confidence: 61%

“…For example, Davies et al [7][8][9] observed that platelets from patients with advanced AD retained intact APP on their surface after thrombin activation in contrast to normal platelets that demonstrated an -secretase-mediated cleavage and release of APP. Further interest in platelets was stimulated by reports documenting that the ratio of two soluble APP (sAPP) isoforms present in platelet -granules is altered in AD [10][11][12], and this alteration in sAPP ratios is predictive of early stage disease and disease progression [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Coated-platelets retain amyloid precursor protein on their surface

et al. 2006

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Coated-Platelets are a subset of platelets produced by dual-agonist activation with collagen plus thrombin and are characterized by strong retention of several procoagulant, alpha-granule proteins on the cell surface. In this report we demonstrate that coated-platelets also retain full-length amyloid precursor protein (APP) on their surface in contrast to the cleavage of APP in platelets activated with a single agonist. In addition, western blot analysis indicated that APP is derivatized during coated-platelet synthesis. We subsequently measured coated-platelet production in patients with Alzheimer's disease (AD). Twenty-two AD patients showed a wide distribution of coated-platelet values; however the least impaired AD patients produced coated-platelets at a level significantly above that of aged controls (41.0 +/- 9.9 vs. 28.7 +/- 11.4%; mean +/- 1SD; p = 0.017). These findings suggest that coated-platelets may be a model of aberrant APP processing in early AD patients.

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Section: Discussioncontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Coated-platelets retain amyloid precursor protein on their surface

et al. 2006

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“…Specifically, Aβ protein accumulated around blood vessels forms the characteristic fiche of Alzheimer’s amyloid angiopathy [33, 34]. Our hypothesis is supported by the fact that activated platelets in AD patients have certain APP-processing abnormalities [35] and that in a transgenic mouse model of AD, platelets were found to be the major contributors of cerebral amyloid angiopathy [36]. Additionally, it was demonstrated that platelet-derived Aβ passes through the endothelial cell layer in a blood–brain barrier model comprised of human cerebrovascular endothelial cells isolated from the brains of patients with AD [37].…”

Section: Introductionmentioning

confidence: 75%

Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis

Kucheryavykh

Dávila-Rodríguez

Rivera-Aponte

et al. 2017

Brain Research Bulletin

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Introduction Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated. Methods We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains. Results Both in vivo results and electron microscopy revealed that platelets were 300–500 times more concentrated in clots than in non-clotted blood. After thrombosis in control mice, but not in thrombocytopenic animals, Aβ immunofluorescence was present inside blood vessels in the visual cortex and around capillaries in the entorhinal cortex. Conclusion The increased concentration of platelets allows enhanced release of Aβ during thrombosis, suggesting an additional source of Aβ in the brains of Alzheimer’s patients that may arise if frequent micro-thrombosis events occur in their brains.

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“…Evidences indicates that platelets contain all the enzymatic machinery to produce metabolites of alpha and beta-secretases and that both APPs and Abeta can be stored and released upon platelet activation [39,40]. Consequently, although unlikely to contribute to cerebral amyloid deposition, platelet APP forms represent an easily accessible peripheral source of human material from which to study APP biochemistry and metabolism both in physiological or in pathological conditions [41,42].…”

Section: Mild Cognitive Impairmentmentioning

confidence: 99%

Combined Biomarkers for Early Alzheimer Disease Diagnosis

Borroni¹,

Premi²,

Luca³

et al. 2007

CMC

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Few public health problems have captured the attention of the biomedical and lay communities alike as has Alzheimer Disease (AD). Several questions remain still open in disease management, as the necessity to delineate disease process from "normal ageing". In the last few years, Mild Cognitive Impairment (MCI) has received significant attention, thus it represents the major risk factor for AD. Not all people diagnosed as having MCI, however, will develop AD, hence there is a need to reliably predict progression. To this aim, different biomarkers have been proposed with the attempt to identify MCI people who already have pre-clinical AD. Neuropsychological assessment, peripheral and CSF biomarkers as well as neuroimaging findings (both structural and functional) have reported variable accuracy values, but better results have been obtained by combined biomarker approach. In this review, we summarise the most recent findings on combined biomarkers and their usefulness in clinical practice for the early and preclinical diagnosis of AD.

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Activated Alzheimer Disease Platelets Retain More Beta Amyloid Precursor Protein

Cited by 52 publications

References 21 publications

Coated-platelets retain amyloid precursor protein on their surface

Coated-platelets retain amyloid precursor protein on their surface

Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis

Combined Biomarkers for Early Alzheimer Disease Diagnosis

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