PMID- 32265636
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 14
DP  - 2020
TI  - Erosion of Gene Co-expression Networks Reveal Deregulation of Immune System 
      Processes in Late-Onset Alzheimer's Disease.
PG  - 228
LID - 10.3389/fnins.2020.00228 [doi]
LID - 228
AB  - We have applied a novel and integrative analysis framework for next-generation 
      sequencing (NGS) data to 503 human subjects provided by the Religious Orders 
      Study and Memory and Aging Project (ROSMAP) to examine changes in transcriptomic 
      organization and common variants in association with late-onset Alzheimer's 
      disease (LOAD). Our framework identified seven reproducible, co-regulated modules 
      after quality control (QC), clinical segregation, preservation filtering, and 
      functional ontology analysis. These modules were specifically enriched in several 
      innate and adaptive immune system processes, the synaptic vesicle cycle, and 
      Hippo signaling. Topological and functional erosion of these modules due to 
      shedding of genes and loss of in-module connectivity was diagnostic of disease 
      progression. Perturbation analysis revealed that only 1% of eQTLs overlapped 
      genes participating in these co-regulated modules. Common variants nevertheless 
      identified components of the immune systems like human leukocyte antigen (HLA) 
      complex and microtubule-associated protein tau (MAPT) regions in association with 
      LOAD. Our results implicate microglial function, adaptive immune response, and 
      the structural degeneration of neurons as contributors to the transcriptional 
      deregulation observed along with common genetic variants in the progression of 
      LOAD.
CI  - Copyright (c) 2020 Malamon and Kriete.
FAU - Malamon, John Stephen
AU  - Malamon JS
AD  - Bossone Research Center, School of Biomedical Engineering, Science and Health 
      Systems, Drexel University, Philadelphia, PA, United States.
FAU - Kriete, Andres
AU  - Kriete A
AD  - Bossone Research Center, School of Biomedical Engineering, Science and Health 
      Systems, Drexel University, Philadelphia, PA, United States.
LA  - eng
PT  - Journal Article
DEP - 20200320
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC7099620
OTO - NOTNLM
OT  - Alzheimer's
OT  - WGCNA
OT  - eQTL
OT  - functional
OT  - immune system
OT  - networks
OT  - synapses
EDAT- 2020/04/09 06:00
MHDA- 2020/04/09 06:01
PMCR- 2020/01/01
CRDT- 2020/04/09 06:00
PHST- 2019/09/06 00:00 [received]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/04/09 06:00 [entrez]
PHST- 2020/04/09 06:00 [pubmed]
PHST- 2020/04/09 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2020.00228 [doi]
PST - epublish
SO  - Front Neurosci. 2020 Mar 20;14:228. doi: 10.3389/fnins.2020.00228. eCollection 
      2020.