Alzheimer's Disease and Ageing: A Chromosomal Approach

Abstract

Alzheimer’s disease (AD) is the most common type of dementia in elderly people. Interrelations between AD and senescence have been the subject of many studies. Some researchers have suggested that chromosomal alterations may be involved in the etiology or pathogenesis of AD. We present cytogenetic findings in patients with Alzheimer’s disease, normal elderly controls and young controls. Aneuploidy, premature centromere division, polyploidy and C-anaphase, were analysed and the results suggest that the cytogenetic alterations observed are inherent to the cellular ageing process and not specifically related to Alzheimer’s disease.

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

“…in peripheral blood lymphocytes, both in AD patients and healthy subjects of same age category. Based on the number of cells with DNA damage and PCD present on any chromosome, the expression of chromosomal instability is more prominent in AD subjects compared to age-matched controls [6,7,8,12,19]. …”

“…In Alzheimer's disease, some features of chromosome instability have been shown in the cells of the nervous system [2,3,4,5], but also in cells of peripheral tissues [6,7,8,9]. Aneuploidy as a form of chromosome instability is a relevant factor in neurodegenerative changes in AD and in ageing [2,8,10,11,12,13] with reports that the number of aneuploid neurons in affected brain regions exceed 20% [14]. …”

“…Indeed, attacking mitotic microtubules motors by excess of Aβ can impair mitosis in neuronal precursor cells, leading to chromosome missegregation and aneuploid neurons [18]. As a kind of chromosomal alteration, phenomenon of premature centromere division (PCD) was observed in sporadic Alzheimer disease (SAD) [6,8,12,19]. PCD represents a loss of control over sequential separation and segregation of chromosome centromeres, characterized by distinctive separation of chromosomes earlier than usual [20,21].…”

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

“…Since MN can contain fragments or whole chromosomes, the application of FISH with the alphoid satellite probe can help to distinguish Previous findings from cytogenetic studies performed to assess chromosomal aberrations in cells of AD patients have been controversial (Ward et al 1979;Nordenson et al 1980;White et al 1981;Kormann-Bortolotto et al 1993). A clear trend of a positive correlation between aneuploidy and both forms of the disease (sporadic and familial) in female AD patients compared with unaffected subjects has been found by Moorhead and Heyman (1983).…”

“…An increase in aneuploid metaphases has been reported (Ward et al 1979;Nordenson et al 1980), but not always confirmed (White et al 1981;Kormann-Bortolotto et al 1993).…”