Abstract
Activation of microglia, the primary mediators of inflammation in the brain, is a major component of gliosis and neuronal loss in a number of age-related neurodegenerative disorders, such as Alzheimer's disease (AD). The role of activated microglia in white matter, and its relationship with cognitive decline during aging are unknown. The current study evaluated microglia densities in the white matter of postmortem specimens from cognitively normal young adults, cognitively normal older adults, and cognitive “SuperAgers,” a unique group of individuals over age 80 whose memory test scores are at a level equal to or better than scores of 50-to-65-year-olds. Whole hemisphere sections from cognitively normal old, young, and “SuperAgers” were used to quantify densities of human leukocyte antigen-D related (HLA-DR)-positive activated microglia underlying five cortical regions. Statistical findings showed a significant main effect of group on differences in microglia density where cognitively normal old showed highest densities. No difference between SuperAgers and young specimens were detected. In two autopsied SuperAgers with MRI FLAIR scans available, prominent hyperintensities in periventricular regions were observed, and interestingly, examination of corresponding postmortem sections showed only sparse microglia densities. In conclusion, activated microglia appear to respond to age-related pathologic changes in cortical white matter, and this phenomenon is largely spared in SuperAgers. Findings offer insights into the relationship between white matter neuroinflammatory changes and cognitive integrity during aging.
| Original language | English (US) |
|---|---|
| Article number | 094 |
| Journal | Frontiers in Aging Neuroscience |
| Volume | 11 |
| Issue number | MAY |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Cognitive aging
- Memory
- Microglia
- Neurodegeneration
- White matter
ASJC Scopus subject areas
- Aging
- Cognitive Neuroscience
Cite this
}
Activated microglia in cortical white matter across cognitive aging trajectories. / Gefen, Tamar Devora; Kim, Garam; Bolbolan, Kabriya; Geoly, Andrew; Ohm, Daniel; Oboudiyat, Carly; Shahidehpour, Ryan; Rademaker, Alfred W; Weintraub, Sandra; Bigio, Eileen H; Mesulam, Marek-Marsel; Rogalski, Emily; Geula, Changiz.
In: Frontiers in Aging Neuroscience, Vol. 11, No. MAY, 094, 01.01.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - Activated microglia in cortical white matter across cognitive aging trajectories
AU - Gefen, Tamar Devora
AU - Kim, Garam
AU - Bolbolan, Kabriya
AU - Geoly, Andrew
AU - Ohm, Daniel
AU - Oboudiyat, Carly
AU - Shahidehpour, Ryan
AU - Rademaker, Alfred W
AU - Weintraub, Sandra
AU - Bigio, Eileen H
AU - Mesulam, Marek-Marsel
AU - Rogalski, Emily
AU - Geula, Changiz
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Activation of microglia, the primary mediators of inflammation in the brain, is a major component of gliosis and neuronal loss in a number of age-related neurodegenerative disorders, such as Alzheimer's disease (AD). The role of activated microglia in white matter, and its relationship with cognitive decline during aging are unknown. The current study evaluated microglia densities in the white matter of postmortem specimens from cognitively normal young adults, cognitively normal older adults, and cognitive “SuperAgers,” a unique group of individuals over age 80 whose memory test scores are at a level equal to or better than scores of 50-to-65-year-olds. Whole hemisphere sections from cognitively normal old, young, and “SuperAgers” were used to quantify densities of human leukocyte antigen-D related (HLA-DR)-positive activated microglia underlying five cortical regions. Statistical findings showed a significant main effect of group on differences in microglia density where cognitively normal old showed highest densities. No difference between SuperAgers and young specimens were detected. In two autopsied SuperAgers with MRI FLAIR scans available, prominent hyperintensities in periventricular regions were observed, and interestingly, examination of corresponding postmortem sections showed only sparse microglia densities. In conclusion, activated microglia appear to respond to age-related pathologic changes in cortical white matter, and this phenomenon is largely spared in SuperAgers. Findings offer insights into the relationship between white matter neuroinflammatory changes and cognitive integrity during aging.
AB - Activation of microglia, the primary mediators of inflammation in the brain, is a major component of gliosis and neuronal loss in a number of age-related neurodegenerative disorders, such as Alzheimer's disease (AD). The role of activated microglia in white matter, and its relationship with cognitive decline during aging are unknown. The current study evaluated microglia densities in the white matter of postmortem specimens from cognitively normal young adults, cognitively normal older adults, and cognitive “SuperAgers,” a unique group of individuals over age 80 whose memory test scores are at a level equal to or better than scores of 50-to-65-year-olds. Whole hemisphere sections from cognitively normal old, young, and “SuperAgers” were used to quantify densities of human leukocyte antigen-D related (HLA-DR)-positive activated microglia underlying five cortical regions. Statistical findings showed a significant main effect of group on differences in microglia density where cognitively normal old showed highest densities. No difference between SuperAgers and young specimens were detected. In two autopsied SuperAgers with MRI FLAIR scans available, prominent hyperintensities in periventricular regions were observed, and interestingly, examination of corresponding postmortem sections showed only sparse microglia densities. In conclusion, activated microglia appear to respond to age-related pathologic changes in cortical white matter, and this phenomenon is largely spared in SuperAgers. Findings offer insights into the relationship between white matter neuroinflammatory changes and cognitive integrity during aging.
KW - Cognitive aging
KW - Memory
KW - Microglia
KW - Neurodegeneration
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85068257758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068257758&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2019.00094
DO - 10.3389/fnagi.2019.00094
M3 - Article
VL - 11
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - MAY
M1 - 094
ER -