Platelet Activation in Alzheimer Disease

Sevush, Steven; Jy, Wenche; Horstman, Lawrence L.; Mao, Wei; Kolodny, Luciano; Ahn, Yeon S.

doi:10.1001/archneur.55.4.530

Cited by 164 publications

(118 citation statements)

References 42 publications

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“…47 Interestingly, it has been reported that AD patients have similar platelet counts as age-matched controls, but their platelets are in a more activated state. 48,49 Whether APP/ sAPPs are responsible for the phenotype in our patient cohort is unknown.…”

Section: Org Frommentioning

confidence: 99%

Abnormal clotting of the intrinsic/contact pathway in Alzheimer disease patients is related to cognitive ability

et al. 2018

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Key Points• Clot initiation and strength are altered in AD patient plasma and transgenic AD mouse model.• Clotting abnormalities are correlated with the cognitive state of AD patients.Alzheimer disease (AD) is a neurodegenerative disorder characterized by extracellular b-amyloid (Ab) deposition. Although peripheral inflammation and cerebrovascular pathology are reported in AD, there is a lack of plasma biomarkers in this field. Because the contact system is triggered in patient plasma, we hypothesized that the hemostasis profile could be a novel biomarker in AD. Here, we assessed the clotting profile in plasma from AD patients and age-matched controls. Utilizing clinically relevant assays, thromboelastography and activated partial thromboplastin time, we found impaired clot initiation and formation rate in AD patient plasma. These coagulation end points correlated with cerebrospinal fluid neurofilament-light levels and cognition and were more profound in younger AD patients. Ex vivo intrinsic clotting of plasma from AD mice expressing human amyloid precursor protein (APP) was also delayed in an age-dependent manner, suggesting that this phenotype is related to APP, the parent protein of Ab. Further analysis of coagulation factors in human plasma indicated that endogenous inhibitor(s) of factors XII and XI in AD plasma contribute to this delayed clotting. Together, these data suggest that delayed clotting in young AD patients is a novel biomarker and that therapies aimed to correct this phenotype might be beneficial in this patient population. Follow-up studies in additional AD patient cohorts are warranted to further evaluate these findings.

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Section: Org Frommentioning

confidence: 99%

Abnormal clotting of the intrinsic/contact pathway in Alzheimer disease patients is related to cognitive ability

et al. 2018

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“…Other case-control studies did not find significant differences in the levels of fibrinogen between patients with vascular dementia or Alzheimer disease and controls. 19,20 To our knowledge, the association of fibrinogen and vascular dementia and Alzheimer disease has not been studied in a large, prospective population-based setting.…”

Section: Van Oijen Et Al Fibrinogen Is Associated With Risk Of Dementmentioning

confidence: 99%

Fibrinogen Is Associated With an Increased Risk of Alzheimer Disease and Vascular Dementia

Oijen

Witteman

Hofman

et al. 2005

Stroke

185

158

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Background and Purpose-Vascular and inflammatory factors may play an important role in the pathogenesis of dementia. Studies reported an association between plasma levels of inflammation markers and the risk of dementia. Both fibrinogen and C-reactive protein are considered inflammatory markers. Fibrinogen also has important hemostatic properties. We investigated the association of fibrinogen and C-reactive protein with dementia. Methods-The study was based on the prospective population-based Rotterdam Study. Fibrinogen was measured in a random sample of 2835 persons. High-sensitivity C-reactive protein was measured in the total cohort of 6713 persons. We identified 395 incident dementia cases during follow-up (mean, 5.7 years). We estimated the associations of fibrinogen and C-reactive protein with dementia using Cox proportional hazard models. Results-Persons with higher levels of fibrinogen had an increased risk of dementia. The hazard ratio for dementia per SD increase of fibrinogen was 1.26 (95% CI, 1.11 to 1.44), adjusted for age and gender, and 1.30 (95% CI, 1.13 to 1.50) after additional adjustment for cardiovascular factors and stroke. For Alzheimer disease, the adjusted hazard ratio was 1.25 (95% CI, 1.04 to 1.49), and for vascular dementia it was 1.76 (95% CI, 1.34 to 2.30). High levels of C-reactive protein were not associated with an increased risk of dementia. Conclusions-High fibrinogen levels were associated with an increased risk of both Alzheimer disease and vascular dementia, but levels of C-reactive protein were not. This suggests that the increased risk of dementia associated with fibrinogen is because of the hemostatic rather than the inflammatory properties of fibrinogen.

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“…1 There is limited case-control evidence associating markers of hemostasis and inflammation with dementia. [2][3][4][5][6] Limited prospective data come from the Rotterdam Study, which found that fibrinogen, but not C-reactive protein (CRP), was associated with incident dementia at the age of 6 years. 7 Therefore, further studies of hemostatic and inflammatory markers and risk of dementia (both vascular and nonvascular) are required.…”

mentioning

confidence: 99%

Is Sticky Blood Bad for the Brain?

Gallacher¹,

Bayer²,

Lowe³

et al. 2010

ATVB

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Objective-Hemostasis and inflammation have been implicated in dementia. This study investigates the role of specific hemostatic and inflammatory pathways with incident vascular and nonvascular dementia. Methods and Results-This was a prospective study of a population sample of men aged 65 to 84 years, with baseline assessment of hemostatic and inflammatory factors and cognition measured 17 years later. The sample included 865 men (59 had dementia and 112 had cognitive impairment, not dementia), free of vascular disease at baseline and for whom hemostatic and inflammatory marker data were available and cognitive status was known. A total of 15 hemostatic and 6 inflammatory markers were assessed. Factor analysis was used to identify hemostatic subsystems. The National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurologie criteria were used to identify vascular dementia. By using standardized (z) scores for hemostatic and inflammatory markers, and after adjustment for age and risk factors, vascular dementia was associated with fibrinogen (hazard ratio Key Words: dementia Ⅲ hemostasis Ⅲ inflammation Ⅲ cognition Ⅲ aging H emostasis and the inflammatory response are complex and interrelated processes that are associated with a variety of phenotypes, including cardiovascular diseases. 1 There is limited case-control evidence associating markers of hemostasis and inflammation with dementia. [2][3][4][5][6] Limited prospective data come from the Rotterdam Study, which found that fibrinogen, but not C-reactive protein (CRP), was associated with incident dementia at the age of 6 years. 7 Therefore, further studies of hemostatic and inflammatory markers and risk of dementia (both vascular and nonvascular) are required. See accompanying article on page 461Hemostasis involves a delicate balance of several closely related subsystems or pathways. It is possible, therefore, that associations with these responses reflect the impact of specific pathways rather than of individual biomarkers. One area of interest is whether hemostatic markers can be analyzed within the context of the coagulation pathways that they represent and whether these pathways can be used to identify more closely the mechanisms associated with cognitive impairment. In the Caerphilly Prospective Study, a wide range of available hemostatic markers allows the comparative influence of several pathways to be assessed. 8 Methods The Study PopulationBetween 1979 and 1983, all men aged 45 to 59 years within the locality of Caerphilly in South Wales, England, were invited to participate. Of the 2818 men found eligible, 2512 (89.1%) were recruited. For the second examination (1985), the original cohort was supplemented with all men of a similar age who had moved into the

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Platelet Activation in Alzheimer Disease

Cited by 164 publications

References 42 publications

Abnormal clotting of the intrinsic/contact pathway in Alzheimer disease patients is related to cognitive ability

Abnormal clotting of the intrinsic/contact pathway in Alzheimer disease patients is related to cognitive ability

Fibrinogen Is Associated With an Increased Risk of Alzheimer Disease and Vascular Dementia

Is Sticky Blood Bad for the Brain?

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