Platelet immunoglobulin and amyloid precursor protein as potential peripheral biomarkers for Alzheimer's disease: findings from a pilot study

Mukaetova‐Ladinska, Elizabeta B.; Abdel-All, Zeinab; Dodds, Steven J.; Andrade, Joana; Silva, Joaquim Alves da; Kalaria, Raj N.; O’Brien, John T.

doi:10.1093/ageing/afr171

Cited by 24 publications

(21 citation statements)

References 27 publications

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“…Several years later, a 110 kDa tau variant was also found in peripheral tissues such as human oral epithelium [192] and rat muscle [193]. Expression of tau protein in human platelets has been reported [56] together with an elevated ratio of high molecular weight (>80 kDa) oligomeric isoform variants to monomeric tau in AD patients [24]. In a follow-up study, this group identified tau modifications also in healthy subjects, without any age dependency.…”

Section: Reviewmentioning

confidence: 99%

“…Nevertheless, the above described ratio seemed to correlate with the cognitive status of AD patients [27]. Other studies analysed platelet tau quantities in AD patients and control subjects but could not detect any disease-specific differences [25, 56]. However, C-terminal end tau protein levels of MCI subjects were significantly different from normal ones.…”

Section: Reviewmentioning

confidence: 99%

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Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers?

Veitinger

Varga

Guterres

et al. 2014

acta neuropathol commun

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Peripheral biomarkers play an indispensable role in quick and reliable diagnoses of any kind of disease. With the population ageing, the number of people suffering from age-related diseases is expected to rise dramatically over the coming decades. In particular, all types of cognitive deficits, such as Alzheimer’s disease, will increase. Alzheimer’s disease is characterised mainly by coexistence of amyloid plaques and neurofibrillary tangles in brain. Reliable identification of such molecular characteristics antemortem, however, is problematic due to restricted availability of appropriate sample material and definitive diagnosis is only possible postmortem. Currently, the best molecular biomarkers available for antemortem diagnosis originate from cerebrospinal fluid. Though, this is not convenient for routine diagnosis because of the required invasive lumbar puncture. As a consequence, there is a growing demand for additional peripheral biomarkers in a more readily accessible sample material. Blood platelets, due to shared biochemical properties with neurons, can constitute an attractive alternative as discussed here. This review summarises potential platelet Alzheimer’s disease biomarkers, their role, implication, and alteration in the disease. For easy comparison of their performance, the Hedge effect size was calculated whenever data were available.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers?

Veitinger

Varga

Guterres

et al. 2014

acta neuropathol commun

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“…Roher et al, 2009). In the search for biomarkers of AD, these two facts have provided a rationale for examining easily obtained peripheral tissues for biomarkers of AD, and APP fragments in blood have received special attention in these studies (Borroni et al, 2010; Takeda et al, 2010; Hampel et al, 2010; Mukaetova-Ladinska, et al, 2012). The APP products circulating in the fluid compartment(s) of blood have a number of potential sources, including from brain, endothelial cells, platelets and leukocytes (e.g.…”

Section: Introductionmentioning

confidence: 99%

Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

Delvaux

Bentley

Stubbs

et al. 2013

Neurobiology of Aging

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Since Amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer’s disease (AD). Using immunohistochemistry, immuno-electron microscopy, Western blotting and quantitative RT-PCR we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blotting data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. ADAM10, nicastrin and BACE2 were present in brain but were undetected in PBL. PS1 and BACE1 were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated where Western and qPCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers.

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“…The ratio of high molecular weight (130 kDa) APP form to that of low molecular weight (110 kDa and 106 kDa) is termed platelet APP form ratio (APPr). It has been shown that alteration of platelet APP processing is an early event in Alzheimer's disease, and APPr measurement might be of diagnostic value in differentiating mild Alzheimer's disease from normal aging Evin and Li, 2012;Mukaetova-Ladinska et al, 2012). Other researchers investigated APP-N expression in platelets, and found that APP-N levels were negatively correlated with cognitive scores (Mukaetova-Ladinska et al, 2012).…”

mentioning

confidence: 99%

“…It has been shown that alteration of platelet APP processing is an early event in Alzheimer's disease, and APPr measurement might be of diagnostic value in differentiating mild Alzheimer's disease from normal aging Evin and Li, 2012;Mukaetova-Ladinska et al, 2012). Other researchers investigated APP-N expression in platelets, and found that APP-N levels were negatively correlated with cognitive scores (Mukaetova-Ladinska et al, 2012). Finally, a recent promising study showed that combination of 18 selected biomarkers (chemokines, cytokines, growth factors and binding proteins) in plasma might allow the diagnosis of Alzheimer's disease (Mangialasche et al, 2013) and MCI with nearly 90% accuracy.…”

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confidence: 99%

Amyloid precursor protein in peripheral granulocytes as a potential biomarker for Alzheimer's disease

Wang¹,

Li²,

Yang³

et al. 2016

Bangladesh J Pharmacol

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The aim of this study was to assess the potential of amyloid precursor protein in peripheral granulocytes as a diagnostic biomarker for early detection of Alzheimers disease. Immunohistochemistry and flow cytometry were used to evaluate amyloid precursor protein expression levels and subcellular localization in Alzheimers disease. Much higher amyloid precursor protein expression was observed in some leukocytes from Alzheimers disease patients, compared with samples from non-Alzheimers disease controls. In addition, flow cytometry data indicated significantly higher amyloid precursor protein expression in granulocytes from Alzheimers disease patients compared with control values. No statistically significant differences in amyloid precursor protein expression were obtained in lymphocytes or monocytes between the patient groups. In conclusion, amyloid precursor protein expression level in peripheral blood granulocyte is a potential biomarker for early diagnosis of Alzheimers disease.

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Platelet immunoglobulin and amyloid precursor protein as potential peripheral biomarkers for Alzheimer's disease: findings from a pilot study

Abstract: these preliminary findings suggest that platelet measures of the traditional biomarkers for AD are feasible in the periphery. The measures of platelet APP-N and Ig, in particular, merit further study in a larger cohort of AD and control subjects.

Cited by 24 publications

References 27 publications

Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers?

Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers?

Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

Amyloid precursor protein in peripheral granulocytes as a potential biomarker for Alzheimer's disease

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