Alzheimer disease and platelets: how’s that relevant

Catricalà, Silvia; Torti, Mauro; Ricevuti, Giovanni

doi:10.1186/1742-4933-9-20

Cited by 116 publications

(92 citation statements)

References 139 publications

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“…Thus, it is necessary to consider the relationship between genetic risk factors and markers for AD pathology for future metabolomics, proteomics and imaging studies38. Moreover, many researchers have discussed evidence for underlying AD mechanisms, including an important relationship between resting state functional connectivity and the resulting distinctive pattern of Aβ plaque deposition in specific brain regions39404142. Thus, we should be able to predict the changes of metabolism in specific regions regarding the deposition of Aβ plaques.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling of Alzheimer's disease brains

Inoue

Tsutsui

Akatsu

et al. 2013

Sci Rep

138

118

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Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

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Section: Discussionmentioning

confidence: 99%

Metabolic profiling of Alzheimer's disease brains

Inoue

Tsutsui

Akatsu

et al. 2013

Sci Rep

138

118

View full text Add to dashboard Cite

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“…APP is an integral membrane protein, made by neurons and other brain cells and is also expressed in extraneural tissues such as pancreas, kidney, and spleen and is abundant in blood platelets. 25 Its function is unknown. Neurotoxic APs are composed predominantly of amyloid-b (Ab) peptides of 40 (Abx-40) and 42 (Abx-42) amino acids in length, formed by sequential cleavage of APP by b-, and g-secretases.…”

Section: Neuropilar Lesionsmentioning

confidence: 99%

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

et al. 2016

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According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases.

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“…For decades, platelets have been considered a good model to study the pathophysiology of AD and a promising source of AD biomarkers, because platelets display all the enzymes of an amyloidogenic pathway and generate Aβ peptides ( Figure 1B) [19]. It has been suggested that full-length APP acts as a receptor on the platelet surface and also appears to be crucial in the regulation of intracellular Ca 2+ concentration [20].…”

Section: Prospective Ad Biomarkers In Plateletsmentioning

confidence: 99%

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

et al. 2017

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Current Alzheimer's disease (AD) diagnostics is based on cognitive testing, and detecting amyloid Aβ and τ pathology by brain imaging and assays of cerebrospinal fluid. However, biomarkers identifying complex pathways contributing to pathology are lacking, especially for early AD. Preferably, such biomarkers should be more cost-effective and present in easily available diagnostic tissues, such as blood. Here, we summarize the recent findings of potential early AD molecular diagnostic biomarkers in blood platelets, lymphocytes and erythrocytes. We review molecular alterations which refer to such main hypotheses of AD pathogenesis as amyloid cascade, oxidative and mitochondrial stress, inflammation and alterations in cell cycle regulatory molecules. The major advantage of such biomarkers is the potential ability to indicate individualized therapies in AD patients. Alzheimer's disease (AD) is the most prevalent age-related dementia worldwide and one of the major unmet, increasing medical and economic problems of the modern world. As of 2015, there were an estimated 46.8 million people with dementia worldwide. This number will increase to an estimated 74.7 million in 2030 [1].Among the neuropathological hallmarks of AD are: the progressive loss of brain neurons, synaptic degeneration and the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) in such regions of the brain as the hippocampus, cortex and amygdala. Amyloid plaques consist mainly of 40-and 42-amino-acid Aβ peptides (Aβ40 and Aβ42). Peptides are proteolytic cleavage products of the Aβ protein precursor (APP) but with no fully elucidated biological function. NFTs are deposits of paired helical filaments composed mainly of hyperphosphorylated τ protein, a microtubule-stabilizing protein that maintains neuronal cell structure and axonal transport. Nevertheless, neither senile plaques nor NFTs are absolute hallmarks of AD dementia, because cognitively intact aged individuals may exhibit both pathological changes upon postmortem brain examination or as assessed by positron emission tomography amyloid and τ imaging agents (amyloid-PET and τ-PET) [2][3][4][5].Clinical AD manifests by aggravating dysfunction and weakening functional cognitive processes, linked to brain neuron loss that is both progressive and permanent [4], and that within several years leads to total dependence on the caregiver and eventually to death. Advances in our knowledge of AD have shown that clinical symptoms usually develop after a long preclinical pathogenic process, lasting for decades, making early AD detection in asymptomatic patients a subject of great interest [4,5]. Increasing proof demonstrates that the therapeutic methods' effectiveness is strictly contingent on the early diagnosis of AD, before the occurrence of massive neuron loss and dementia. This highlights the key importance of biochemical biomarkers for early AD diagnostics. AD diagnostics & demand for novel, improved biomarkersThe broadly accepted recommendations for AD diagnosis...

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Alzheimer disease and platelets: how’s that relevant

Cited by 116 publications

References 139 publications

Metabolic profiling of Alzheimer's disease brains

Metabolic profiling of Alzheimer's disease brains

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

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