English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background While Alzheimer disease (AD) is generally considered as a brain disorder, blood biomarkers may be useful for the diagnosis and prediction of AD brain pathology. The  APOE  ε4 allele has shown cerebrovascular effects including acceleration of blood-brain barrier (BBB) breakdown. Methods We evaluated the differential expression of previously established AD genes in brains from 344 pathologically confirmed AD cases and 232 controls and in blood from 112 pathologically confirmed AD cases and 67 controls from the Religious Orders Study and Memory and Aging Project. Differential gene expression between AD cases and controls was analyzed in the blood and brain jointly using a multivariate approach in the total sample and within  APOE  genotype groups. Gene set enrichment analysis was performed within  APOE  genotype groups using the results from the combined blood and brain analyses to identify biologically important pathways. Gene co-expression networks in brain and blood samples were investigated using weighted correlation network analysis. Top-ranked genes from networks and pathways were further evaluated with vascular injury traits. Results We observed differentially expressed genes with  P  &lt; 0.05 in both brain and blood for established AD genes  INPP5D  (upregulated) and  HLA-DQA1  (downregulated).  PIGHP1  and  FRAS1  were differentially expressed at the transcriptome-wide level ( P  &lt; 3.3 × 10 −6 ) within ε2/ε3 and ε3/ε4 groups, respectively. Gene set enrichment analysis revealed 21 significant pathways (false discovery rate  P  &lt; 0.05) in at least one  APOE  genotype group. Ten pathways were significantly enriched in the ε3/ε4 group, and six of these were unique to these subjects. Four pathways (allograft rejection, interferon gamma response, peroxisome, and TNFA signaling via NFKB) were enriched for AD upregulated genes in the ε3/ε4 group and AD downregulated genes in subjects lacking ε4. We identified a co-expressed gene network in the brain that reproduced in blood and showed higher average expression in ε4 carriers. Twenty-three genes from pathway and network analyses were significantly associated with at least one vascular injury trait. Conclusion These results suggest that the  APOE  genotype contributes to unique expression network profiles in both blood and brain. Several genes in these networks are associated with measures of vascular injury and potentially contribute to ε4’s effect on the BBB.

Blood and brain transcriptome analysis reveals APOE genotype-mediated and immune-related pathways involved in Alzheimer disease