Dementia and Aging-Associated Changes in the Human Brain Transcriptome.
Human Amyloid Imaging Abstract. 2012 Jan 1;
Most studies of gene expression in the aged brain have focused on disease related changes including those associated with Alzheimer’s disease. In addition to insights into disease processes, the study of global gene expression in multiple regions of the normal human brain and comparison of gene expression in young-old (85 years) can provide insights into mechanisms that contribute to successful cognitive aging.
Genome-wide gene expression was studied across 17 brain regions of 130 non-demented individuals and persons dying at different stages of dementia and Alzheimer’s disease progression.
Gene expression changes in the temporal and prefrontal cortices are more closely related to disease severity than other regions examined; the degree of gene expression change in a given region varied depending on the disease severity classification scheme used; the classification of cases by CDR provides a more orderly gradient of gene expression change in most brain regions than groupings based on neuropathological indices. In non-demented persons, 332 probe sets showed significantly altered expression in the oldest-old (older than 85 years) relative to cognitively intact young-old persons. Strikingly, all transcripts among genes whose expression was altered by dementia and aging were upregulated in cognitively intact oldest-old persons relative to cognitively intact young-old persons. Gene ontology classification of these common probe sets from the two age categories showed them to be linked to canonical immune function pathways.
The results suggest that gene expression varies with brain region, dementia severity and severity of AD neuropathology. Successful aging to advanced old-age is associated with a robust and preserved CNS immune response system. It is possible that persons who survive to advanced old age with intact cognition are those individuals whose CNS immune system is able to respond to and defend against physiological insults (e.g., amyloidogenic, cardiovascular) effectively.