TY - JOUR
T1 - Glial cytoplasmic inclusions in neurologically normal elderly
T2 - Prodromal multiple system atrophy?
AU - Fujishiro, Hiroshige
AU - Ahn, Tae Beom
AU - Frigerio, Roberta
AU - DelleDonne, Anthony
AU - Josephs, Keith A.
AU - Parisi, Joseph E.
AU - Eric Ahlskog, J.
AU - Dickson, Dennis W.
N1 - Funding Information:
Acknowledgments Supported by NIH grants P50-AG16574, P50-NS40256 and R01-AG15866, PaciWc Alzheimer Research Foundation (PARF) grant C06-01.
PY - 2008
Y1 - 2008
N2 - In this study, we used immunohistochemistry to screen for α-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multiple system atrophy (MSA), a non-familial neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction and α-synuclein immunoreactive glial cytoplasmic inclusions (GCI). In a routine hospital autopsy series of 125 brains, we detected GCI in a neurologically normal 82-year-old man (0.8%). Both cases showed widespread GCI in the central nervous system, as well as a few neuronal cytoplasmic inclusions, but no neuronal loss or gliosis in vulnerable brain regions, including the substantia nigra, putamen, inferior olive and pontine base. Applying a recently proposed grading scale for MSA, the two cases showed pathology far below that detected in patients with clinically overt MSA, suggesting the possibility that these two individuals had preclinical MSA. The prevalence of clinically overt MSA is estimated to be about 4 per 100,000 persons (0.004%), which is far less than the frequency of GCI in this series (0.4-0.8%). Further studies are needed to determine if GCI in neurologically normal elderly represents prodromal MSA or a rare non-progressive age-related α-synucleinopathy.
AB - In this study, we used immunohistochemistry to screen for α-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multiple system atrophy (MSA), a non-familial neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction and α-synuclein immunoreactive glial cytoplasmic inclusions (GCI). In a routine hospital autopsy series of 125 brains, we detected GCI in a neurologically normal 82-year-old man (0.8%). Both cases showed widespread GCI in the central nervous system, as well as a few neuronal cytoplasmic inclusions, but no neuronal loss or gliosis in vulnerable brain regions, including the substantia nigra, putamen, inferior olive and pontine base. Applying a recently proposed grading scale for MSA, the two cases showed pathology far below that detected in patients with clinically overt MSA, suggesting the possibility that these two individuals had preclinical MSA. The prevalence of clinically overt MSA is estimated to be about 4 per 100,000 persons (0.004%), which is far less than the frequency of GCI in this series (0.4-0.8%). Further studies are needed to determine if GCI in neurologically normal elderly represents prodromal MSA or a rare non-progressive age-related α-synucleinopathy.
KW - Clinicopathologic
KW - Glial cytoplasmic inclusion
KW - Multiple system atrophy
KW - Preclinical
KW - α-Synuclein
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U2 - 10.1007/s00401-008-0398-7
DO - 10.1007/s00401-008-0398-7
M3 - Article
C2 - 18553090
AN - SCOPUS:49049110031
SN - 0001-6322
VL - 116
SP - 269
EP - 275
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 3
ER -