WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease
Ana Rajicic Lucia A A Giannini Emma Gerrits Renee van Buuren Shamiram Melhem Johan A Slotman Annemieke J M Rozemuller Bart J L Eggen John C van Swieten Harro Seelaar 王晶
WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease
Ana Rajicic 1Lucia A A Giannini 1Emma Gerrits 2Renee van Buuren 1Shamiram Melhem 1Johan A Slotman 3Annemieke J M Rozemuller 4Bart J L Eggen 5John C van Swieten 1Harro Seelaar 1王晶
扫码查看
点击上方二维码区域，可以放大扫码查看
作者信息
1. Department of Neurology and Alzheimer Centre Erasmus MC,Erasmus MC University Medical Center,Rotterdam,the Netherlands
2. Department of Neuroscience,Karolinska Institutet,Stockholm,Sweden
3. Department of Pathology and Erasmus Optical Imaging Center,Erasmus MC University Medical Center,Rotterdam,the Netherlands
4. Department of Pathology,Amsterdam Neuroscience,Amsterdam University Medical Center,Amsterdam,The Netherlands
5. Department of Biomedical Sciences of Cells&Systems,Section of Molecular Neurobiology,University of Groningen and University Medical Center Groningen,Groningen,Netherlands
A subpopulation of astrocytes expressing WD Repeat Domain 49(WDR49)was recently identified in fronto-temporal lobar degeneration(FTLD)with GRN pathogenic variants.This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease(AD).In a postmortem cohort of TDP-43 pro-teinopathies(12 GRN,11 C9orf72,9 sporadic TDP-43),tauopathies(13 MAPT,8 sporadic tau),10 AD,and four con-trols,immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on fron-tal,temporal,and occipital cortical sections.WDR49-positive cell counts(adjusted per mm2)were examined and related to digitally quantified percentage areas of TDP-43/tau pathology and semiquantitative scores of neurodegeneration.Quantitative colocalization analysis of WDR49 and pathological inclusions was done.WDR49-positive astrocytes were present across FTLD subtypes and AD in the brain parenchyma and(peri-)vascular space,with distinct morphological patterns,and were particularly enriched in gray matter.In controls,sporadic WDR49-positive cells were found envelop-ing vessels.WDR49-positive astrocytes were most abundant in the frontal cortex(FC)of GRN cases and temporal cor-tex in GRN,AD,and sporadic primary tauopathy.In the occipital cortex,only a few cells were found across groups.WDR49-positive astrocyte counts positively correlated with the severity of neurodegeneration and TDP-43 pathology but not tauopathy.Furthermore,in frontotemporal cortices,WDR49 partly colocalized with TDP-43(14%-21%)and tau(31%-45%).In conclusion,WDR49 is a marker for a subset of astrocytes with different morphologies across FTLD and AD,reflecting the severity of neurodegeneration.These astrocytes may become activated in neurodegeneration in re-sponse to pathological damage and migrate from the vessel wall to the parenchyma.
维普
万方数据