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

Abstract

Fluorescence in situ hybridization (FISH) is the method of choice for visualizing chromosomal DNA in post-mitotic cells. The availability of chromosome-enumeration (centromeric), site-specific, and multicolor-banding DNA probes offers opportunities to uncover genomic changes, at the chromosomal level, in single interphase nuclei. Alzheimer's disease (AD) has been associated repeatedly with (sub)chromosome instability and aneuploidy, likely affecting the brain. Although the types and rates of chromosome instability in the AD brain remain a matter of debate, molecular cytogenetic analysis of brain cells appears to be important for uncovering mechanisms of neurodegeneration. Here, we describe a FISH protocol for studying chromosome instability and aneuploidy in the AD brain.

Keywords: Alzheimer’s disease; Aneuploidy; Brain; Chromosome instability; DNA probes; FISH; Fluorescence in situ hybridization; ICS-MCB; Interphase chromosome-specific multicolor banding; Interphase nuclei; Molecular neurocytogenetic analysis.