Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.
PPA
Alzheimer's disease
Cortical atrophy
TDP-43
White matter pathology
activated microglia
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
02
08
2017
accepted:
02
04
2018
pubmed:
22
4
2018
medline:
20
8
2020
entrez:
22
4
2018
Statut:
ppublish
Résumé
Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.
Identifiants
pubmed: 29679378
doi: 10.1111/nan.12494
pmc: PMC6196127
mid: NIHMS962034
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
216-229Subventions
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056258
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC008552
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS095652
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG020506
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS075075
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS085770
Pays : United States
Informations de copyright
© 2018 British Neuropathological Society.
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