Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease

Migliore, Lucia; Testa, Anna; Scarpato, Roberto; Pavese, Nicola; Petrozzi, Lucia; Bonuccelli, Ubaldo

doi:10.1007/s004390050632

Cited by 88 publications

(66 citation statements)

References 41 publications

(52 reference statements)

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“…An increase in trisomy 21 and trisomy 17 has been reported in buccal cells in AD cases when compared to their respective controls (11). Furthermore micronuclei are a biomarker of chromosome malsegregation and tend to be elevated in lymphocytes, fibroblasts and buccal cells of AD cases (8,28,29). Other DNA damage markers such as cH2AX (DNA double strand breaks) and 8HOdG (oxidative DNA damage) were also found to be linked with AD (30)(31)(32) and previously detected in human buccal cells (33,34).…”

Section: Discussionmentioning

confidence: 73%

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

et al. 2014

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Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to measure buccal cell type ratios, nuclear DNA content and shape, and neutral lipid content of buccal cells from clinically diagnosed AD (n 5 13) and MCI (n 5 13) patients prior to treatment compared to age-and gender-matched controls (n 5 26). DNA content was significantly higher in all cell types in both MCI (P < 0.01) and AD (P < 0.05) compared with controls mainly due to an increase in >2N nuclei. Abnormal nuclear shape (circularity) was significantly increased in transitional cells in MCI (P < 0.001) and AD (P < 0.01) when compared to controls. In contrast, neutral lipid content (as measured by Oil red O "ORO" staining) of buccal cells was significantly lower in the MCI group (P < 0.05) compared with the control group. The ratio of DNA content/ORO in buccal basal cells for both MCI and AD was significantly higher compared to the control group, with ratios for MCI being approximately 2.8-fold greater (P < 0.01) and AD approximately 2.3-fold greater (P < 0.05) than the control group. Furthermore, there was a strong negative correlation between buccal cell DNA content and ORO content in the AD group (r 2 5 0.75, P < 0.0001) but not in MCI or controls. The changes in the buccal cell cytome observed in this study could prove useful as potential biomarkers in identifying individuals with an increased risk of developing MCI and eventually AD. V C 2014 International Society for Advancement of Cytometry

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Section: Discussionmentioning

confidence: 73%

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

et al. 2014

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“…Considering the parallel between the increase in MN frequency and early Alzheimer symptoms, one could hypothesize that the increase in MN frequency observed could be related to early progression of AD in the DS individuals evaluated, which warrants further study. Given this fact, alterations in the cell kinetics or structural profile of the buccal mucosa, including MN frequency changes, have been shown in AD (Migliore et al, 1997;Trippi et al, 2001;Petrozzi et al, 2002;, and may be useful as potential biomarkers in identifying individuals with a high risk of developing AD . Therefore, the possibility to apply the MN assay in the detection of AD risk, opening a new application for the MN assay, has already been suggested for identifying individuals with high risk of cancer (Bonassi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Buccal micronucleus frequency is associated with age in Down syndrome

Ferreira

Prá²,

Martino-Roth³

et al. 2009

Genet. Mol. Res.

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ABSTRACT. Down syndrome has been linked to premature aging and genomic instability. We examined the frequency of micronucleus (MN) and binucleated cells in the oral mucosa of Down syndrome patients and healthy controls matched by age and gender, addressing the effect of age and family income. Down syndrome individuals had an increased number of MN (14.30 ± 9.35 vs 4.03 ± 1.71; P < 0.001) and binucleated cells (0.97 ± 1.3 vs 0.33 ± 0.66; P < 0.05) per 2000 cells. Micronucleus frequency of Down syndrome individuals correlated positively with age (r = 0.437; P = 0.009), and the older (≥21) Down syndrome age group (30.8 ± 8.4 years old) had about 2-fold more micronuclei (P ≤ 0.05) than did the younger group (<21). Average family income did not correlate with MN frequency in controls (r = -0.948; P = 0.183), but a borderline negative correlation was seen in DS subjects (r = -0.9484; P = 0.0516). Individuals whose average income was ten times minimum wages had about 2-fold less MN than those receiving around minimum wage. We conclude that the buccal MN assay is a useful and minimally invasive method for monitoring genetic damage in humans and could be used as a tool to evaluate ageassociated genomic instability in Down syndrome.

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“…There is substantial evidence supporting the fact that genetic instability is increased in AD lymphocytes compared to corresponding controls. An important aspect of genetic research related to AD is the analysis of lymphocytes chromosome instability which in cludes: aneuploidies of different chromosomes, telo mere shortening and the phenomenon of premature centomere division (31)(32)(33). Also, an im paired DNA repair mechanism, particularly the base excision re pair pathway, might play an essential role in Alzheimer's disease (34).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of DNA Damage in the Lymphocytes of Young, Elderly and Alzheimer’s Disease Patients Treated with β-Estradiol in the Comet Assay

Žrsković¹,

Djelić²,

Bajićs³

et al. 2013

Journal of Medical Biochemistry

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Summary Background: The antioxidant activity of estrogen has a be ne - ficial impact in Alzheimer’s disease. A variety of clinical stu - dies have demonstrated that estrogen replacement therapy in postmenopausal women results in a lower frequency of AD, delaying the onset of the neurodegenerative cascade. On the other hand, it has been demonstrated that estrogens may exhibit genotoxic effects, especially at elevated tissue concentrations. Therefore, the aim of this study was to determine whether b-estradiol induces DNA damage in the peripheral blood lymphocytes of healthy young females and males, healthy elderly females and males and females and males with Alzheimer’s disease. Methods: All experiments were performed using the alkaline version of the Comet assay (single cell gel electrophoresis), on six donors per each experimental group and controls. Results: In the Comet assay, a significant increase of DNA migration was observed in the lymphocytes of all treated groups (young and elderly females, young and elderly males, AD females and AD males) at all b-estradiol concentrations (50 mmol/L, 100 mmol/L and 250 mmol/L) used in this investigation. In all the experiments cell viability was over 80%. Conclusions: Lymphocytes are sensitive to the test concentrations of b-estradiol in the Comet assay regardless of gender, age and health condition of the examined subjects. Therefore, the role of b-estradiol in cellular DNA damage has been confirmed.

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Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease

Cited by 88 publications

References 41 publications

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

Buccal micronucleus frequency is associated with age in Down syndrome

Evaluation of DNA Damage in the Lymphocytes of Young, Elderly and Alzheimer’s Disease Patients Treated with β-Estradiol in the Comet Assay

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