ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects

Manzine, Patrícia Regina; Marcello, Elena; Borroni, Barbara; Kamphuis, Willem; Hol, Elly M.; Padovani, Alessandro; Nascimento, Carla Manuela Crispim; Bueno, Patrícia; Vale, Francisco Assis Carvalho; Pavarini, Sofía Cristina Iost; Luca, Mónica Di; Cominetti, Márcia Regina

doi:10.3109/1354750x.2015.1062554

Cited by 27 publications

(15 citation statements)

References 32 publications

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“…A reduced level of ADAM10 is observed in platelets obtained from AD and MCI patients compared with age-matched controls [25].…”

Section: Prospective Ad Biomarkers In Plateletsmentioning

confidence: 99%

“…In AD platelets from AD patients, changes in the ratio between different isoforms of APP were reported, which correlated with a cognitive decline [24,25]. While alternative splicing of the APP gene can generate at least ten different mRNAs, the isoform predominantly expressed in neuronal tissues is APP695, whereas in non-neuronal cells the most abundant isoforms are APP751 and APP770 [24].…”

Section: Prospective Ad Biomarkers In Plateletsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Med. (2017) 11(10) future science group Search for Alzheimer's disease biomarkers in blood cells: hypotheses-driven approach Review Furthermore, a qualitatively and quantitatively similar decrease in sAPPα is present both in thrombin-activated platelets and the CSF, thus suggesting that alterations of APP processing might occur both in the neuronal compartment and peripheral cells [25].Another study also suggested APP as potential platelet AD biomarker, but this time on the platelet surface, related to coated-platelets [26]. Coated platelets (formerly known as COAT-platelets), represent a subpopulation of cells observed after dual agonist stimulation of platelets with collagen and thrombin.…”

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confidence: 99%

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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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“…A reduced level of ADAM10 is observed in platelets obtained from AD and MCI patients compared with age-matched controls [25].…”

Section: Prospective Ad Biomarkers In Plateletsmentioning

confidence: 99%

Section: Prospective Ad Biomarkers In Plateletsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2017

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“…For example, the genetic variants in the gene SORL1 have been shown to associate with the age at onset of AD [57], [58], while ADAM10 gene encodes the major a-secretase responsible for cleaving APP in families with late-onset AD [59], [60]. In addition, DAPK1 plays an important role in neuronal apoptosis and could affect the pathology of late-onset AD [61], [62].…”

Section: Methodsmentioning

confidence: 99%

Low-Rank Graph-Regularized Structured Sparse Regression for Identifying Genetic Biomarkers

Zhu

Suk

Huang

et al. 2017

IEEE Trans. Big Data

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In this paper, we propose a novel sparse regression method for Brain-Wide and Genome-Wide association study. Specifically, we impose a low-rank constraint on the weight coefficient matrix and then decompose it into two low-rank matrices, which find relationships in genetic features and in brain imaging features, respectively. We also introduce a sparse acyclic digraph with sparsity-inducing penalty to take further into account the correlations among the genetic variables, by which it can be possible to identify the representative SNPs that are highly associated with the brain imaging features. We optimize our objective function by jointly tackling low-rank regression and variable selection in a framework. In our method, the low-rank constraint allows us to conduct variable selection with the low-rank representations of the data; the learned low-sparsity weight coefficients allow discarding unimportant variables at the end. The experimental results on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset showed that the proposed method could select the important SNPs to more accurately estimate the brain imaging features than the state-of-the-art methods.

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Current and Developing Methods for Diagnosing Alzheimer's Disease

Fuller

Carrigan

Sohrabi

et al. 2019

Neurodegeneration and Alzheimer's Disease

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ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects

Cited by 27 publications

References 32 publications

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

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

Low-Rank Graph-Regularized Structured Sparse Regression for Identifying Genetic Biomarkers

Current and Developing Methods for Diagnosing Alzheimer's Disease

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