title: Cortical Transcriptional Profiles in APOE4 Carriers with Alzheimer's Disease: Patterns of Protection and Degeneration.
abstract: Transcriptional profiling of postmortem Alzheimer's disease (AD) brain tissue has yielded important insights into disease. We recently described a novel approach to understand transcriptional changes in AD designed to identify both neuro-susceptibility and intrinsic neuroprotective factors in young non-AD E4 carriers. Here we extend our work to APOE4 related AD itself. In temporal cortex (BA 21), a region known to be vulnerable to AD pathology, we identified over 1400 transcripts that differed between APOE4 controls and APOE4 carriers diagnosed with AD. Results from somatosensory cortex (BA 1/2/3), a region relatively preserved in AD differed strikingly from temporal cortex in that differences were far fewer (37 vs. 1492). We also conducted another set of contrasts involving APOE3 AD cases and APOE4 AD cases to better understand what transcriptional differences were dependent on genotype, but independent of disease status and found 6 transcripts to differ. We also conducted detailed pathway analyses in BA 1/2/3 and found significant transcriptional upregulations in pro-survival gene networks (e.g., TNF and NFkB). In summary, our results indicate that many of the molecular changes identified in the brains of patients with AD reflect the non-specific consequences of neurodegeneration, rather than causative processes. Additionally, the molecular signatures specific to somatosensory cortex may make it uniquely resistant to AD pathology and thereby could provide important leads for treatment.
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Concepcion
authors.initials: C
authors.lastname: Conejero-Goldberg
authors.affiliation: Neuropathology Section, Lieber Institute for Brain Development, Baltimore, MD, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hyde
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Shufen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Neuropathology Section, GCAP, IRP, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Herman
authors.affiliation: Neuropathology Section, Lieber Institute for Brain Development, Baltimore, MD, USA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Kleinman
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D060005:Genotyping Techniques; D066128:Gray Matter / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D013003:Somatosensory Cortex / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
chemical_list: D053327:Apolipoprotein E4
keywords: APOE; Alzheimer’s disease; gene expression; human brain; microarray