Systems genetic dissection of Alzheimer’s disease brain gene expression networks

SYNOPSISMessenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

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O4-10-03: FUNCTIONAL DISSECTION OF ALZHEIMER'S DISEASE BRAIN GENE EXPRESSION SIGNATURES IN HUMANS AND MOUSE MODELS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.4796 ◽

2019 ◽

Vol 15 ◽

pp. P1260-P1260

Author(s):

Carl Grant Mangleburg ◽

Ying-Wooi Wan ◽

Rami Al-Ouran ◽

Tom V. Lee ◽

Katherine S. Allison ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Models ◽

Brain Gene Expression ◽

Gene Expression Signatures

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Heterogeneity of Brain Gene Expression in Alzheimer's Disease

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1993.tb18297.x ◽

1993 ◽

Vol 679 (1 Markers of Ne) ◽

pp. 178-187 ◽

Cited By ~ 2

Author(s):

JOHN R. DUGUID ◽

CHRISTOPHER TRZEPACZ ◽

THOMAS KEMPER ◽

WALLACE W. TOURTELLOTE ◽

LADISLAV VOLICER

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Gene Expression

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Genome-Wide Integrative Analysis Reveals Common Molecular Signatures in Blood and Brain of Alzheimer’s Disease

Biointerface Research in Applied Chemistry ◽

10.33263/briac112.86868701 ◽

2020 ◽

Vol 11 (2) ◽

pp. 8686-8701

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enrichment Analysis ◽

Integrative Analysis ◽

Gene Set Enrichment Analysis ◽

Brain Gene Expression ◽

Sensitivity Specificity ◽

Eqtl Data ◽

Brain Tissues

The currently utilized neuroimaging and cerebrospinal fluid-based detection of Alzheimer’s disease (AD) suffer several limitations, including sensitivity, specificity, and cost. Therefore, the identification of AD by analyzing blood gene expression may ameliorate the early diagnosis of the AD. We aimed to identify common genes commonly deregulated in blood and brain in AD. Comprehensive analysis of blood and brain gene expression datasets of AD, eQTL, and epigenetics data was analyzed by the integrative bioinformatics approach. The integrative analysis showed nine differentially expressed genes common to blood cells and brain (CNBD1, SUCLG2-AS1, CCDC65, PDE4D, MTMR1, C3, SLC6A15, LINC01806, and FRG1JP). Analysis of SNP and cis-eQTL data showed 18 genes; namely, HSD17B1, GAS5, RPS5, VKORC1, GLE1, WDR1, RPL12, MORN1, RAD52, SDR39U1, NPHP4, MT1E, SORD, LINC00638, MCM3AP-AS1, GSDMD, RPS9, and GNL2 were observed deregulated AD blood and brain tissues. Functional gene set enrichment analysis demonstrated a significant association of these genes in neurodegeneration-associated molecular pathways. Integrative biomolecular networks revealed dysregulation of several hub transcription factors and microRNAs in AD. Moreover, hub genes were observed associated with significant histone modification. This study detected common molecular biomarkers and pathways in blood and brain tissues in AD that may be potential biomarkers and therapeutic targets in AD.

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