TY - JOUR
T1 - Astrocytic degeneration in chronic traumatic encephalopathy
AU - Hsu, Eric T.
AU - Gangolli, Mihika
AU - Su, Shiran
AU - Holleran, Laurena
AU - Stein, Thor D.
AU - Alvarez, Victor E.
AU - McKee, Ann C.
AU - Schmidt, Robert E.
AU - Brody, David L.
N1 - Publisher Copyright:
© 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated head traumas. Using immunohistochemistry for glial fibrillary acidic protein as a marker, plus automated quantitative analysis, we examined the characteristics and extent of astrogliosis present in stage III and IV CTE, along with Alzheimer’s disease (AD), and frontotemporal dementia (FTD) cases. Astrogliosis in CTE patients was more diffuse compared to that of AD and FTD patients, which was concentrated in the sulcal depths. Of 14 patients with CTE, 10 exhibited signs of a degenerating astrocyte pathology, characterized by beaded, broken astrocytic processes. This astrocytic degeneration was typically found to be diffuse throughout the white matter, although two cases demonstrated astrocytic degeneration in the gray matter. The degeneration was also observed in 2 of 3 AD and 2 of 3 FTD brains, with overall similar characteristics across diseases. There was minimal to no astrocytic degeneration in six age-matched controls with no neurodegenerative disease. We found that the extent of the white matter astrocytic degeneration was strongly correlated with the level of overall astrogliosis in both the white and gray matter. However, astrocytic degeneration was not correlated with the overall extent of tau pathology. Specifically, there was no correlation between levels of p-tau in the sulcal depths and astrocytic degeneration in the white matter adjacent to the sulcal depths. Thus, astrocytic degeneration and overall astrogliosis appear to represent distinct pathological features of CTE. Further investigation into these astroglial pathologies could provide new insights into underlying disease mechanisms and represent a potential target for in vivo assessment of CTE as well as other neurodegenerative disorders.
AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated head traumas. Using immunohistochemistry for glial fibrillary acidic protein as a marker, plus automated quantitative analysis, we examined the characteristics and extent of astrogliosis present in stage III and IV CTE, along with Alzheimer’s disease (AD), and frontotemporal dementia (FTD) cases. Astrogliosis in CTE patients was more diffuse compared to that of AD and FTD patients, which was concentrated in the sulcal depths. Of 14 patients with CTE, 10 exhibited signs of a degenerating astrocyte pathology, characterized by beaded, broken astrocytic processes. This astrocytic degeneration was typically found to be diffuse throughout the white matter, although two cases demonstrated astrocytic degeneration in the gray matter. The degeneration was also observed in 2 of 3 AD and 2 of 3 FTD brains, with overall similar characteristics across diseases. There was minimal to no astrocytic degeneration in six age-matched controls with no neurodegenerative disease. We found that the extent of the white matter astrocytic degeneration was strongly correlated with the level of overall astrogliosis in both the white and gray matter. However, astrocytic degeneration was not correlated with the overall extent of tau pathology. Specifically, there was no correlation between levels of p-tau in the sulcal depths and astrocytic degeneration in the white matter adjacent to the sulcal depths. Thus, astrocytic degeneration and overall astrogliosis appear to represent distinct pathological features of CTE. Further investigation into these astroglial pathologies could provide new insights into underlying disease mechanisms and represent a potential target for in vivo assessment of CTE as well as other neurodegenerative disorders.
KW - Astrocyte
KW - Chronic traumatic encephalopathy
KW - Glial fibrillary acidic protein
KW - Neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=85052969608&partnerID=8YFLogxK
U2 - 10.1007/s00401-018-1902-3
DO - 10.1007/s00401-018-1902-3
M3 - Article
C2 - 30194648
AN - SCOPUS:85052969608
SN - 0001-6322
VL - 136
SP - 955
EP - 972
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 6
ER -