TY - JOUR
T1 - Transcriptome Changes in the Alzheimer's Disease Middle Temporal Gyrus
T2 - Importance of RNA Metabolism and Mitochondria-Associated Membrane Genes
AU - Piras, Ignazio S.
AU - Krate, Jonida
AU - Delvaux, Elaine
AU - Nolz, Jennifer
AU - Mastroeni, Diego F.
AU - Persico, Antonio M.
AU - Jepsen, Wayne M.
AU - Beach, Thomas G.
AU - Huentelman, Matthew J.
AU - Coleman, Paul D.
AU - Combs, Colin
N1 - Funding Information:
1. The Mayo Clinic Brain Bank. Data collec-tion was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, R01 AG003949, NINDS grant R01 NS080820, CurePSP Foundation, and support from Mayo Foundation.
Funding Information:
We are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human biological materials (brain tissue). The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer’s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson’s Disease Consortium) and the Michael J. Fox Foundation for Parkinson’s Research.
Funding Information:
We thank the National Institutes of Health, National Institute on Aging for support by grant R01 AG O36400 to PDC.
Publisher Copyright:
© 2019 - IOS Press and the authors. All rights reserved.
PY - 2019
Y1 - 2019
N2 - We used Illumina Human HT-12 v4 arrays to compare RNA expression of middle temporal gyrus (MTG; BA21) in Alzheimer's disease (AD=97) and non-demented controls (ND=98). A total of 938 transcripts were highly differentially expressed (adj p<0.01; log2 FC ≥ |0.500|, with 411 overexpressed and 527 underexpressed in AD. Our results correlated with expression profiling in neurons from AD and ND obtained by laser capture microscopy in MTG from an independent dataset (log2 FC correlation: r=0.504; p=2.2e-16). Additionally, selected effects were validated by qPCR. ANOVA analysis yielded no difference between genders in response to AD, but some gender specific genes were detected (e.g., IL8 and AGRN in males, and HSPH1 and GRM1 in females). Several transcripts were associated with Braak staging (e.g., AEBP1 and DNALI1), antemortem MMSE (e.g., AEBP1 and GFAP), and tangle density (e.g., RNU1G2, and DNALI1). At the pathway level, we detected enrichment of synaptic vesicle processes and GABAergic transmission genes. Finally, applying the Weighted Correlation Network Analysis, we identified four expression modules enriched for neuronal and synaptic genes, mitochondria-associated membrane, chemical stimulus and olfactory receptor and non-coding RNA metabolism genes. Our results represent an extensive description of MTG mRNA profiling in a large sample of AD and ND. These data provide a list of genes associated with AD, and correlated to neurofibrillary tangles density. In addition, these data emphasize the importance of mitochondrial membranes and transcripts related to olfactory receptors in AD.
AB - We used Illumina Human HT-12 v4 arrays to compare RNA expression of middle temporal gyrus (MTG; BA21) in Alzheimer's disease (AD=97) and non-demented controls (ND=98). A total of 938 transcripts were highly differentially expressed (adj p<0.01; log2 FC ≥ |0.500|, with 411 overexpressed and 527 underexpressed in AD. Our results correlated with expression profiling in neurons from AD and ND obtained by laser capture microscopy in MTG from an independent dataset (log2 FC correlation: r=0.504; p=2.2e-16). Additionally, selected effects were validated by qPCR. ANOVA analysis yielded no difference between genders in response to AD, but some gender specific genes were detected (e.g., IL8 and AGRN in males, and HSPH1 and GRM1 in females). Several transcripts were associated with Braak staging (e.g., AEBP1 and DNALI1), antemortem MMSE (e.g., AEBP1 and GFAP), and tangle density (e.g., RNU1G2, and DNALI1). At the pathway level, we detected enrichment of synaptic vesicle processes and GABAergic transmission genes. Finally, applying the Weighted Correlation Network Analysis, we identified four expression modules enriched for neuronal and synaptic genes, mitochondria-associated membrane, chemical stimulus and olfactory receptor and non-coding RNA metabolism genes. Our results represent an extensive description of MTG mRNA profiling in a large sample of AD and ND. These data provide a list of genes associated with AD, and correlated to neurofibrillary tangles density. In addition, these data emphasize the importance of mitochondrial membranes and transcripts related to olfactory receptors in AD.
KW - Alzheimer's disease
KW - Microarray
KW - Middle temporal gyrus
KW - Postmortem brains
KW - RNA profiling
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U2 - 10.3233/JAD-181113
DO - 10.3233/JAD-181113
M3 - Article
C2 - 31256118
AN - SCOPUS:85066962654
SN - 1387-2877
VL - 70
SP - 691
EP - 713
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 3
ER -