FISHing for Chromosome Instability and Aneuploidy in the Alzheimer’s Disease Brain

Yurov, Yuri B.; Vorsanova, Svetlana G.; Iourov, Ivan Y.

doi:10.1007/978-1-0716-2655-9_10

Cited by 5 publications

(2 citation statements)

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“…Nonetheless, a large body of work has indicated that as individuals age, a small population of these cells may recommit to a cell cycle-like process [ 4 ], and increasing levels of these events are found in disease-affected brains of patients with late-onset Alzheimer’s disease (AD) [ 4 – 11 ]. While the reprogression and completion of the entire process of mitosis has never been reported, evidence related to the reexpression of cell cycle proteins [ 6 – 11 ] and somatic copy number variations (CNVs) [ 12 ] have been found [ 13 – 15 ], suggesting that a partial duplication of genomic materials might have co-occurred even though this process is likely prematurely halted by the activation of cell cycle checkpoint signaling through the physiological surveillance response [ 16 ]. While some studies have suggested that the rapid reexpression of cell cycle-related genes in neurons immediately leads to cell death and apoptosis [ 17 , 18 ], other reports have indicated that this phenomenon is instead a possible driver of the cellular senescence response [ 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence

Wu,

Sun,

Chow

2024

PLoS Biol

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Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear. Through a bioinformatics approach that allows integrated analyses of multiple single-nucleus transcriptome datasets from human brain samples, these rare cell populations were identified and selected for further characterization. Our analyses indicated that these cell cycle-related events occur predominantly in excitatory neurons and that cellular senescence is likely their immediate terminal fate. Quantitatively, the number of cell cycle re-engaging and senescent neurons decreased during the normal brain aging process, but in the context of late-onset Alzheimer’s disease (AD), these cells accumulate instead. Transcriptomic profiling of these cells suggested that disease-specific differences were predominantly tied to the early stage of the senescence process, revealing that these cells presented more proinflammatory, metabolically deregulated, and pathology-associated signatures in disease-affected brains. Similarly, these general features of cell cycle re-engaging neurons were also observed in a subpopulation of dopaminergic neurons identified in the Parkinson’s disease (PD)-Lewy body dementia (LBD) model. An extended analysis conducted in a mouse model of brain aging further validated the ability of this bioinformatics approach to determine the robust relationship between the cell cycle and senescence processes in neurons in this cross-species setting.

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Section: Introductionmentioning

confidence: 99%

Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence

Wu,

Sun,

Chow

2024

PLoS Biol

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“…fluorescent in situ hybridization (FISH) in individual neurons of AD patients' brain(Yurov et al, 2023), as well as experimental studies on mice with knockdown of one allele of the BMI1 gene (encodes a protein of the Polycomb group and regulates compaction of heterochromatin).…”

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confidence: 99%

Involvement of transposable elements in Alzheimer’s disease pathogenesis

Mustafin,

Khusnutdinova

2024

Vestn. VOGiS

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Alzheimer’s disease affects an average of 5 % of the population with a significant increase in prevalence with age, suggesting that the same mechanisms that underlie aging may influence this pathology. Investigation of these mechanisms is promising for effective methods of treatment and prevention of the disease. Possible participants in these mechanisms are transposons, which serve as drivers of epigenetic regulation, since they form species-specific distributions of non-coding RNA genes in genomes in evolution. Study of miRNA involvement in Alzheimer’s disease pathogenesis is relevant, since the associations of protein-coding genes (APOE4, ABCA7, BIN1, CLU, CR1, PICALM, TREM2) with the disease revealed as a result of GWAS make it difficult to explain its complex pathogenesis. Specific expression changes of many genes were found in different brain parts of Alzheimer’s patients, which may be due to global regulatory changes under the influence of transposons. Experimental and clinical studies have shown pathological activation of retroelements in Alzheimer’s disease. Our analysis of scientific literature in accordance with MDTE DB revealed 28 miRNAs derived from transposons (17 from LINE, 5 from SINE, 4 from HERV, 2 from DNA transposons), the expression of which specifically changes in this disease (decreases in 17 and increases in 11 microRNA). Expression of 13 out of 28 miRNAs (miR-151a, -192, -211, -28, -31, -320c, -335, -340, -378a, -511, -576, -708, -885) also changes with aging and cancer development, which indicates the presence of possible common pathogenetic mechanisms. Most of these miRNAs originated from LINE retroelements, the pathological activation of which is associated with aging, carcinogenesis, and Alzheimer’s disease, which supports the hypothesis that these three processes are based on the primary dysregulation of transposons that serve as drivers of epigenetic regulation of gene expression in ontogeny.

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