Transactivation response DNA-binding protein 43 microvasculopathy in frontotemporal degeneration and familial Lewy body disease.
We describe novel transactivation response DNA-binding protein of 43 kd (TDP-43)-positive structures in the brains of patients with frontotemporal lobar degeneration with ubiquitin-positive inclusions and familial Lewy body disease. The TDP-43 immunohistochemistry revealed small round structures closely associated with small blood vessels. By immunoelectron microscopy, these TDP-43-positive structures were unmyelinated cell processes located adjacent to and sometimes enclosed by the capillary basal lamina. Some processes protruded from outside of the vascular basal lamina to a position beneath the basal lamina. The processes contained 10- to 17-nm-diameter straight filaments or filaments coated with granular material similar to those described in neurites in frontotemporal lobar degeneration with ubiquitin-positive inclusions and other disorders. In some of the abnormal structures, electron-dense material formed paracrystalline arrays composed of TDP-43. The inclusions were variably positive by immunostaining for the small heat shock protein alphaB-crystallin and less often glial fibrillary acidic protein. Bundles of astrocytic glial fibrils characteristic of reactive astrocytes were often found in proximity, but glial fibrils were negative for TDP-43. These data suggest that these processes are astrocytic end-feet with abnormal TDP-43 fibrillary inclusions. The significance of this novel TDP-43 microvasculopathy on blood-brain barrier integrity warrants further investigation.
Lin
Wen-Lang
WL
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Castanedes-Casey
Monica
M
Dickson
Dennis W
DW
D019943:Amino Acid Substitution / Q000235:genetics; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008833:Microcirculation / Q000235:genetics; D009154:Mutation; D015533:Transcriptional Activation / Q000235:genetics
D004268:DNA-Binding Proteins