Activated microglia in cortical white matter across cognitive aging trajectories

Tamar Devora Gefen*, Garam Kim, Kabriya Bolbolan, Andrew Geoly, Daniel Ohm, Carly Oboudiyat, Ryan Shahidehpour, Alfred W Rademaker, Sandra Weintraub, Eileen H Bigio, Marek-Marsel Mesulam, Emily Rogalski, Changiz Geula

*Corresponding author for this work

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number094
JournalFrontiers in Aging Neuroscience
Volume11
Issue numberMAY
DOIs
StatePublished - Jan 1 2019

Fingerprint

Microglia
Inflammation Mediators
Gliosis
HLA Antigens
Cognitive Aging
White Matter
Neurodegenerative Diseases
Young Adult
Autopsy
Alzheimer Disease
Magnetic Resonance Imaging
Brain

Keywords

  • Cognitive aging
  • Memory
  • Microglia
  • Neurodegeneration
  • White matter

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

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title = "Activated microglia in cortical white matter across cognitive aging trajectories",
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.",
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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 journalArticle

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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

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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.

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KW - Memory

KW - Microglia

KW - Neurodegeneration

KW - White matter

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