Abstract
Structural variation in the human genome is likely to be an important mechanism for neuronal diversity and brain disease. A combination of multiple different forms of aneuploid cells due to loss or gain of whole chromosomes giving rise to cellular diversity at the genomic level have been described in neurons of the normal and diseased adult human brain. Here, we describe recent advances in molecular neuropathology based on the combination of slide-based cytometry with molecular biological techniques that will contribute to the understanding of genetic neuronal heterogeneity in the CNS and its potential impact on Alzheimer's disease and age-related disorders.
Highlights
Structural variation in the human genome is likely to be an important mechanism for neuronal diversity and brain disease
A combination of multiple different forms of aneuploid cells due to loss or gain of whole chromosomes giving rise to cellular diversity at the genomic level have been described in neurons of the normal and diseased adult human brain [1,2,3,4,5,6,7,8,9,10,11]
While a portion of these aneuploid cells apparently die during development [7,23,24], aneuploid neurons have been identified in the mature brain in all areas assayed [3,4,5,6,7,8,11,25] indicating that aneuploidy does not necessarily impair viability [26]
Summary
Understanding the mechanisms underlying generation of neuronal variability and complexity remains a basic challange to neuroscience. A combination of multiple different forms of aneuploid cells due to loss or gain of whole chromosomes (mosaic aneuploidy) giving rise to cellular diversity at the genomic level have been described in neurons of the normal and diseased adult human brain [1,2,3,4,5,6,7,8,9,10,11]. A major drawback of these initial studies on aneuploidy in the adult human brain is the fact that for technical reasons, analyses are performed on isolated cellular nuclei This prevents clear attribution of cytogenetic changes to define subsets of cells and to study these changes in a cytoarchitectonic context of preserved tissue architecture. Each type of chromosome complement abnormality might possess a different propensity for apoptotic clearance
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