Astrocytes degenerate in frontotemporal dementia: possible relation to hypoperfusion.
To understand the extent and specificity of astrocyte pathology in sporadic frontotemporal dementia (FTD), we examined several FTD cases for molecular and morphologic characteristics of astrocyte degeneration. We quantified reactive and degenerating astrocytes in sections of frontal, temporal, parietal, and occipital cortex identified using glial fibrillary acidic protein (GFAP) immunoreactivity, terminal deoxynucleotidyl transferase (TdT) labeling, and morphological characteristics and compared them with nondemented, age-matched control brains. Conventional and confocal microscopy revealed that a subpopulation of GFAP(+) astrocytes exhibited positive TdT labeling and beading of their processes in the frontal, temporal, and parietal cortices in 5 of 7 FTD cases that also exhibited gliosis. This morphology was reproduced in cultured astrocytes using ischemic insults. Degenerating astrocytes in FTD correlated inversely with cerebral blood flow as measured by single photon emission computed tomography (SPECT) analysis of (133)Xe inhalation (r = 0.55, p < 0.05). Furthermore, areas of significant astrogliosis corresponded to areas of SPECT hypoperfusion, suggesting that astrocytes may be affected by or perhaps have a causal role in the disturbances of cerebral perfusion in FTD.
Martin
J A
JA
Alzheimer's Disease Research Center, University of California at Irvine, Irvine, CA 92697-4540, USA. jamx@uci.edu
Craft
D K
DK
Su
J H
JH
Kim
R C
RC
Cotman
C W
CW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D053938:DNA Fragmentation; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D003704:Dementia / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000473:pathology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000032:analysis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D015899:Tomography, Emission-Computed, Single-Photon
D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D004253:DNA Nucleotidylexotransferase