Chromosomal Alterations in Patients with Alzheimer Disease in Manaus, Amazonas, Brazil

Abstract

Alzheimer disease (AD) is a complex neurodegenerative pathology that is characterized by a cognitive decline. Its causes and mechanisms are still largely unknown. It has been suggested that both genetic and life exposure factors can contribute to AD development. There are also evidences that chromosomal alterations can be related to this disease. So far, there is not a precise diagnosis for AD, which is given only after the exclusion of other dementia by clinical and neurological examination. The possible association of AD with chromosomal alterations and the easy access of classical cytogenetics analysis are important aspects to consider, given the difficulties in diagnosis. Due to the lack of similar studies in Brazil and the increasing number of AD cases in the state of Amazonas, the aim of this study was to investigate the presence of chromosomal alterations in patients diagnosed with AD in Manaus, Amazonas, Brazil. Peripheral blood lymphocytes of twelve patients and twelve healthy individuals with the same age were analyzed using conventional karyotyping. All AD patients presented cells with autosomal aneuploidy, while no chromosomal alterations were found in the age-matched controls. Also, rare events of double and multiple aneuploidies are being reported in association with AD for the first time. Our results corroborate that the increase in the frequencies of aneuploidies is not related to the aging process itself, but it might be associated to the disease development. However, no chromosomes were preferentially affected in all AD patients, and no consistent karyotype pattern for AD lymphocytes was found. Therefore, our results do not support the use of standard cytogenetics as a tool for AD diagnosis. Future studies are necessary to understand better the association between chromosomal alterations and AD.

Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders

“…Taken together, these findings provide evidence that aneuploidy can arise de novo in mature neurons by cell cycle reactivation or can be carried over from previously dividing cells that generate new neurons. It is reasonable that age may exacerbate all of these processes because neuronal and non-neuronal aneuploidy have been shown to increase with age (Arendt et al, 2009; Yurov et al, 2009; Yurov et al, 2010; Fischer et al, 2012; Fantin et al, 2019). Aging is also associated with increasing total exposure to environmental stressors, some of which can promote chromosome missegregation and aneuploidy (for reviews, see Potter, 1991; Iourov et al, 2013).…”