Premature centromere division of metaphase chromosomes in peripheral blood lymphocytes of Alzheimer's disease patients: relation to gender and age

Abstract

Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.

Figure 1.

Alzheimer's disease (AD) cases of both genders significantly demonstrate increased PCD,C and PCD,A in peripheral blood lymphocytes compared with controls (A and C). Gender-related differences were found in the percentage of PCD,X, which only was affected in women (B). Female participants, both control and AD, had higher frequency of PCD,C and PCD,X than their corresponding male groups (A and B), which was not the case with PCD,A (C). The data are expressed as mean ± SEM (n = 11–13), and statistically significant differences are labeled. For each participant, 100 metaphase nuclei were analyzed.

Figure 2.

The frequency of premature centromere division (PCD) does not correlate with age in either the Alzheimer's disease (AD) or the control cohorts for PCD,C (A), PCD,X (B), and PCD,A (C) in males or females.

Figure 3.

Representative chromosomes from peripheral blood lymphocytes, G banded, from a control female (B) and an Alzheimer's disease (AD) female showing a normal X chromosome and an X chromosome with PCD,X (A).