PMID- 36062157
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220907
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 14
DP  - 2022
TI  - Accelerated aging-related transcriptome alterations in neurovascular unit cells 
      in the brain of Alzheimer's disease.
PG  - 949074
LID - 10.3389/fnagi.2022.949074 [doi]
LID - 949074
AB  - Alzheimer's disease (AD) is the most common cause of dementia with no effective 
      therapies. Aging is a dominant risk factor for AD. The neurovascular unit (NVU) 
      plays an important role in maintaining homeostasis of the brain microenvironment. 
      The accelerated aging of NVU cells may directly impair NVU function and 
      contribute to AD pathogenesis. However, the expression patterns of aging-related 
      genes (AGs) in NVU cells of AD remain unclear. In this study, we performed 
      single-nucleus transcriptome analysis of 61,768 nuclei from prefrontal cortical 
      samples of patients with AD and normal control (NC) subjects. Eight main cell 
      types were identified, including astrocytes, microglia, excitatory neurons, 
      inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, pericytes, 
      and endothelial cells. Transcriptomic analysis identified the expression patterns 
      of AGs in NVU cells of AD. Gene set enrichment analysis confirmed the key 
      aging-associated cellular pathways enriched in microglia and oligodendrocytes. 
      These aging-related transcriptomic changes in NVU were cross-validated using bulk 
      transcriptome data. The least absolute shrinkage and selection operator 
      regression method was used to select the crucial AGs most associated with AD: 
      IGF1R, MXI1, RB1, PPARA, NFE2L2, STAT5B, FOS, PRKCD, YWHAZ, HTT, MAPK9, HSPA9, 
      SDHC, PRKDC, and PDPK1. This 15-gene model performed well in discriminating AD 
      from NC samples. Among them, IGF1R, MXI1, PPARA, YWHAZ, and MAPK9 strongly 
      correlated with pathologic progression in AD, were identified as critical 
      regulators of AD. Although most AGs showed similar trends of expression changes 
      in different types of NVU cells in AD, certain AGs were expressed in a 
      cell-specific manner. Our comprehensive analysis of brain NVU from patients with 
      AD reveals previously unknown molecular changes associated with aging that may 
      underlie the functional dysregulation of NVU, providing important insights for 
      exploring potential cell-specific therapeutic targets to restore brain 
      homeostasis in AD.
CI  - Copyright (c) 2022 Zhao, Xie and Liu.
FAU - Zhao, Yan
AU  - Zhao Y
AD  - Department of Geriatrics, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Aging and Age-Related Disease Research, Central South University, 
      Changsha, China.
FAU - Xie, Yong-Zhi
AU  - Xie YZ
AD  - Department of Radiology, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Liu, You-Shuo
AU  - Liu YS
AD  - Department of Geriatrics, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Aging and Age-Related Disease Research, Central South University, 
      Changsha, China.
LA  - eng
PT  - Journal Article
DEP - 20220818
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC9435434
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - aging
OT  - neurodegenerative disease
OT  - neurovascular unit
OT  - single-nucleus RNA sequencing
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/06 06:00
MHDA- 2022/09/06 06:01
PMCR- 2022/01/01
CRDT- 2022/09/05 04:21
PHST- 2022/05/20 00:00 [received]
PHST- 2022/07/28 00:00 [accepted]
PHST- 2022/09/05 04:21 [entrez]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/06 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2022.949074 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2022 Aug 18;14:949074. doi: 10.3389/fnagi.2022.949074. 
      eCollection 2022.