Microglia in frontotemporal lobar degeneration with progranulin or C9ORF72 mutations

Autor: Neill R. Graff-Radford, Kevin F. Bieniek, Nobutaka Sakae, Matt Baker, Koji Kasanuki, Marka van Blitterswijk, Melissa E. Murray, Leonard Petrucelli, Dennis W. Dickson, Rosa Rademakers, Shanu F. Roemer
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Pathology
medicine.medical_specialty
Neurosciences. Biological psychiatry. Neuropsychiatry
tau Proteins
Hippocampal formation
Apraxia
White matter
03 medical and health sciences
0302 clinical medicine
Progranulins
C9orf72
Cortex (anatomy)
mental disorders
medicine
Humans
RC346-429
Research Articles
Aged
Aged
80 and over
Microglia
C9orf72 Protein
business.industry
General Neuroscience
nutritional and metabolic diseases
Brain
Neurofibrillary Tangles
Frontotemporal lobar degeneration
Middle Aged
medicine.disease
nervous system diseases
030104 developmental biology
medicine.anatomical_structure
Mutation
Immunohistochemistry
Female
Neurology. Diseases of the nervous system
Human medicine
Neurology (clinical)
Frontotemporal Lobar Degeneration
business
030217 neurology & neurosurgery
RC321-571
Research Article
Zdroj: Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology, Vol 6, Iss 9, Pp 1782-1796 (2019)
ISSN: 2328-9503
Popis: Objective To identify clinicopathological differences between frontotemporal lobar degeneration (FTLD) due to mutations in progranulin (FTLD-GRN) and chromosome 9 open reading frame 72 (FTLD-C9ORF72). Methods We performed quantitative neuropathologic comparison of 17 FTLD-C9ORF72 and 15 FTLD-GRN with a focus on microglia. For clinical comparisons, only cases with high quality medical documentation and concurring diagnoses by at least two neurologists were included (14 FTLD-GRN and 13 FTLD-C9ORF72). Neuropathological analyses were limited to TDP-43 Type A to assure consistent assessment between the groups, acknowledging that Type A is a minority of C9ORF72 patients. Furthermore, only cases with sufficient tissue from all regions were studied (11 FTLD-GRN and 11 FTLD-C9ORF72). FTLD cases were also compared to age- and sex-matched normal controls. Immunohistochemistry was performed for pTDP-43, IBA-1, CD68, and GFAP. Morphological characterization of microglia was performed in sections of cortex blinded to clinical and genetic information. Results FTLD-GRN patients had frequent asymmetric clinical features, including aphasia and apraxia, as well as more asymmetric cortical atrophy. Neuropathologically, FTLD-C9ORF72 had greater hippocampal tau pathology and more TDP-43 neuronal cytoplasmic inclusions. FTLD-GRN had more neocortical microvacuolation, as well as more IBA-1-positive ameboid microglia in superficial cortical layers and in subcortical white matter. FTLD-GRN also had more microglia with nuclear condensation, possibly indicating apoptosis. Microglial morphology with CD68 immunohistochemistry in FTLD-GRN and FTLD-C9ORF72 differed from controls. Interpretation Our findings underscore differences in microglial response in FTLD-C9ORF72 and FTLD-GRN as shown by significant differences in ameboid microglia in gray and white matter. These results suggest the differential contribution of microglial dysfunction in FTLD-GRN and FTLD-C9ORF72 and suggest that clinical, neuroimaging and pathologic differences could in part be related to differences in microglia response.
Databáze: OpenAIRE
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