Advances in the Study of Brain Aging and Alzheimer’s Disease Using Microarray and Next-Generation Sequencing: Focus on Selective Neuronal Vulnerability
Pp. 233-270 (38)
Xinkun Wang, Mary L. Michaelis and Elias K. Michaelis
Pivotal brain functions, such as neurotransmission, cognition, and memory,
decline with advancing age and, especially, in neurodegenerative conditions associated
with aging, such as Alzheimer’s disease (AD). Yet, deterioration in structure and
function of the nervous system during aging or in AD is not uniform throughout the
brain. Selective neuronal vulnerability (SNV) is a general but sometimes overlooked
characteristic of brain aging and AD. There is little known at the molecular level to
account for the phenomenon of SNV. Functional genomic analyses, through unbiased
whole genome expression studies, could lead to new insights into a complex process
such as SNV. Microarray and next-generation sequencing (RNA-Seq) data generated
thus far (as of March 2012) using both human brain tissue and brains from animal
models of aging and AD were analyzed in this chapter. Convergent trends that have
emerged from these data sets were considered in identifying possible molecular and
cellular pathways involved in SNV. It appears that during normal brain aging and in
AD, neurons vulnerable to injury or cell death are characterized by significant decreases
in the expression of genes related to mitochondrial metabolism and energy production.
In AD, vulnerable neurons also exhibit down-regulation of genes related to synaptic
neurotransmission and vesicular transport, cytoskeletal structure and function, and
neurotrophic factor activity. A prominent category of genes that are up-regulated in AD
are those related to inflammatory response and some components of calcium signaling.
These genomic differences between sensitive and resistant neurons can now be used to
explore the molecular underpinnings of previously suggested mechanisms of cell injury
in aging and AD.
Alzheimer’s disease, bioinformatics, biological pathway, brain aging,
calcium signaling, cytoskeleton, energy metabolism, gene expression, gene
ontology, genome, genomics, microarray, mitochondrion, neurobiology, neurodegeneration, neurodegenerative disease, neuroinflammation, neurotrophic
factor, next-generation sequencing, oxidative stress, selective neuronal vulnerability,
synaptic neurotransmission, systems biology, transcriptome.
Higuchi Biosciences Center, The University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA.