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Current Alzheimer Research (1)
Fenech, Michael (2)
Leifert, Wayne (2)
Darzynkiewicz, Zbigniew (1)
Henriksen, Mel (1)
Holden, Elena (1)
Luther, Ed (1)
Martins, Ralph (1)
Smolewski, Piotr (1)
Thomas, Philip (1)
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Laser scanning cytometry for automation of the micronucleus assay
Laser scanning cytometry (LSC) provides a novel approach for automated scoring of micronuclei (MN) in different types of mammalian cells, serving as a biomarker of genotoxicity and mutagenicity. In this review, we discuss the advances to date in measuring MN in cell lines, buccal cells and erythrocytes, describe the advantages and outline potential challenges of this distinctive approach of analysis of nuclear anomalies. The use of multiple laser wavelengths in LSC and the high dynamic range of fluorescence and absorption detection allow simultaneous measurement of multiple cellular and nuclear features such as cytoplasmic area, nuclear area, DNA content and density of nuclei and MN, protein content and density of cytoplasm as well as other features using molecular probes. This high-content analysis approach allows the cells of interest to be identified (e.g. binucleated cells in cytokinesis-blocked cultures) and MN scored specifically in them. MN assays in cell lines (e.g. the CHO cell MN assay) using LSC are increasingly used in routine toxicology screening. More high-content MN assays and the expansion of MN analysis by LSC to other models (i.e. exfoliated cells, dermal cell models, etc.) hold great promise for robust and exciting developments in MN assay automation as a high-content high-throughput analysis procedure.
Biomarkers of Alzheimer’s Disease Risk in Peripheral Tissues; Focus on Buccal Cells
Current Alzheimer Research
Alzheimer’s disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need for minimally invasive tests could be achieved by targeting surrogate tissues, since it is now well recognized that AD is not only a disorder restricted to pathology and biomarkers within the brain. Human buccal cells for instance are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that may be indicative of accelerated ageing or neurodegenerative disorders such as AD. However, to our knowledge there is no review available in the literature covering the biology of buccal cells and their applications in AD biomarker research. Therefore, the aim of this review is to summarize some of the main findings of biomarkers reported for AD in peripheral tissues, with a further focus on the rationale for the use of the buccal mucosa (BM) for biomarkers of AD and the evidence to date of changes exhibited in buccal cells with AD.
Alzheimer’s disease; buccal mucosa; diagnosis; mild cognitive impairment; peripheral biomarkers.
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