Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Astrocyte Senescence as a Component of Alzheimer's Disease
PloS one, v 7(9), pp e45069-e45069
12 Sep 2012
PMID: 22984612
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aging is the main risk factor for Alzheimer's disease (AD); however, the aspects of the aging process that predispose the brain to the development of AD are largely unknown. Astrocytes perform a myriad of functions in the central nervous system to maintain homeostasis and support neuronal function. In vitro, human astrocytes are highly sensitive to oxidative stress and trigger a senescence program when faced with multiple types of stress. In order to determine whether senescent astrocytes appear in vivo, brain tissue from aged individuals and patients with AD was examined for the presence of senescent astrocytes using p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of senescence. Compared with fetal tissue samples (n=4), a significant increase in p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n=6; P=0.02) and 78 to 90 years (n=11; P, 10(-6)). In addition, the frontal cortex of AD patients (n=15) harbored a significantly greater burden of p16(INK4a)-positive astrocytes compared with non-AD adult control subjects of similar ages (n=25; P=0.02) and fetal controls (n=4; P, 10(-7)). Consistent with the senescent nature of the p16(INK4a)-positive astrocytes, increased metalloproteinase MMP-1 correlated with p16(INK4a). In vitro, beta-amyloid 1-42 (A beta(1-42)) triggered senescence, driving the expression of p16(INK4a) and senescence-associated beta-galactosidase. In addition, we found that senescent astrocytes produce a number of inflammatory cytokines including interleukin-6 (IL-6), which seems to be regulated by p38MAPK. We propose that an accumulation of p16(INK4a)-positive senescent astrocytes may link increased age and increased risk for sporadic AD.
Metrics
Details
- Title
- Astrocyte Senescence as a Component of Alzheimer's Disease
- Creators
- Rekha Bhat - Drexel UniversityElizabeth P. Crowe - Drexel UniversityAlessandro Bitto - Drexel UniversityMichelle Moh - Drexel UniversityChristos D. Katsetos - Drexel UniversityFernando U. Garcia - Drexel UniversityFrederick Bradley Johnson - University of PennsylvaniaJohn Q. Trojanowski - University of PennsylvaniaChristian Sell - Drexel UniversityClaudio Torres - Drexel University
- Publication Details
- PloS one, v 7(9), pp e45069-e45069
- Publisher
- Public Library Science
- Number of pages
- 10
- Grant note
- AG022443; AG022443-S1 / National Institutes of Health/National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Resident Research Fellowship Drexel University College of Medicine Aging Initiative Fellowship, Drexel University College of Medicine R01AG022443 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Medical Student Summer Research Fellowship R01NS078283 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Department of Pathology, Drexel University College of Medicine
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Neurobiology and Anatomy; Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000308738500113
- Scopus ID
- 2-s2.0-84866316014
- Other Identifier
- 991019168649604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences