High prevalence of thorn-shaped astrocytes in the aged human medial temporal lobe
Introduction
The tauopathies are a heterogeneous group of degenerative diseases that affect the human central nervous system. The defining brain lesions of tauopathies are intracellular inclusions consisting of abnormally phosphorylated and aggregated microtubule-associated protein tau (for review: Refs. [11], [30], [38], [41]). The most frequently occurring disorder associated with tau pathology is Alzheimer’s disease (AD). Tau pathology in AD mainly affects nerve cells, whereas glial cells are affected only to a slight extent. In other tauopathies, however, tau pathology not only afflicts neurons but also neuroectodermal glial cells [13], [27]. Glial tau pathology is a hallmark, for example, of some families affected by frontotemporal dementia and parkinsonism linked to mutations of the tau gene on chromosome 17 (FTDP-17) [17], [39]. In argyrophilic grain disease (AGD), glial tau pathology typically develops in the cortex and white matter of limbic and hypothalamic brain regions [3], [10], [36]. Tau-positive astrocytic plaques are considered pathognomonic for corticobasal degeneration (CBD) [13], [14], [15], [16]. In progressive supranuclear palsy (PSP) astroglial tau pathology preferentially occurs in the form of tufted astrocytes [40], [44], [45].
Another distinct type of glial fibrillary tangles has been designated as thorn-shaped astrocytes (TSA) [26]. TSA preferentially are distributed throughout subpial, subependymal, and perivascular areas of basal brain structures. TSA have no apparent disease specificity and their pathophysiological and clinical implications are unknown [13]. To date, no comprehensive studies have been performed to examine the age-related prevalence of TSA. The present study investigates the prevalence of TSA in the mediobasal temporal lobe (MTL), which is a major predilection site of TSA formation [26]. After focusing on this region, we report a surprisingly high prevalence of TSA in brains of elderly individuals.
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Materials and methods
Brains from 100 autopsy cases, ranging in age from 42 to 97 years (mean age: 65 years; 46 males, 54 females) were examined (Table 1). All brains were obtained from the Department of Forensic Medicine, affiliated with the University of Frankfurt, between the years 1999 and 2001. After autopsy, the brains were conventionally fixed in a 4% aqueous, non-buffered solution of formaldehyde. Alzheimer-related neurofibrillary changes were classified according to consensus recommendations for the
Results
TSA were preferentially distributed in subpial, perivascular, and subependymal areas of the basal MTL (Fig. 1, Fig. 2). No apparent spatial relationship was noted between TSA and Alzheimer-related neurofibrillary changes or β-amyloid deposition. TSA were detected by the Gallyas silver technique as well as by the antibodies AT8, Alz-50, PHF-1, and TG3. Immunostaining with AT8 appeared to be more sensitive for labeling the TSA-associated changes when compared to PHF-1, TG3, and Alz-50
Discussion
The present study reports a high prevalence of TSA in brains of elderly individuals in the basal MTL. TSA were absent in individuals younger than 60 years of age. By comparison, TSA affected almost every second brain older than 75 years of age. In the oldest group, comprised of 90–99-year-old individuals, the prevalence of TSA increased to a maximum of 62%. These data strongly suggest that TSA are among the most prevalent types of tau-positive intracellular inclusions that develop in the aged
Acknowledgements
This study was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Bundesministerium für Forschung und Technologie. The skillful technical assistance of A. Biczysko, H. Korff, U. Fertig, and M. Babl is gratefully acknowledged. The antibodies PHF-1, TG3, and Alz-50 were kindly provided by Dr. Peter Davis (Albert Einstein College of Medicine, NY).
References (45)
- et al.
Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding
Neuron
(1993) - et al.
Frequency of stages of Alzheimer-related lesions in different age categories
Neurobiol. Aging
(1997) - et al.
Tau protein isoforms phosphorylation and role in neurodegenerative disorders
Brain Res. Brain Res. Rev.
(2000) - et al.
Signature tau neuropathology in gray and white matter of corticobasal degeneration
Am. J. Pathol.
(2002) - et al.
Improved method facilitates reliable APOE genotyping of genomic DNA extracted from formaldehyde-fixed pathology specimens
J. Neurosci. Methods
(1998) - et al.
Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau
J. Biol. Chem.
(1992) - et al.
Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration
Neuron
(2002) - et al.
Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer’s disease-related neurofibrillary changes
Neuroscience
(1995) - et al.
Age-related progression of tau pathology in brains of baboons
Neurobiol. Aging
(2000) - et al.
Tau protein pathology in neurodegenerative diseases
Trends Neurosci.
(1998)
The distribution of tau in the mammalian central nervous system
J. Cell Biol.
Astrocytes expressing hyperphosphorylated tau protein without glial fibrillary tangles in argyrophilic grain disease
Acta Neuropathol. (Berl.)
A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads
Acta Neuropathol. (Berl.)
Neuropil threads occur in dendrites of tangle-bearing nerve cells
Neuropathol. Appl. Neurobiol.
Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia
Neuropathol. Appl. Neurobiol.
Neuropathological stageing of Alzheimer-related changes
Acta Neuropathol. (Berl.)
Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections
Brain Pathol.
Argyrophilic grain disease: frequency of occurrence in different age categories and neuropathological diagnostic criteria
J. Neural. Transm.
Alzheimer’s plaques and tangles: a controlled and enhanced silver-staining method
Soc. Neurosci. Abstr.
Glial inclusions in CNS degenerative diseases
J. Neuropathol. Exp. Neurol.
Neurodegenerative disorders with extensive tau pathology: a comparative study and review
Ann. Neurol.
Neuropathologic overlap of progressive supranuclear palsy, Pick’s disease and corticobasal degeneration
J. Neuropathol. Exp. Neurol.
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