Elsevier

Neurobiology of Aging

Volume 25, Issue 3, March 2004, Pages 397-405
Neurobiology of Aging

High prevalence of thorn-shaped astrocytes in the aged human medial temporal lobe

https://doi.org/10.1016/S0197-4580(03)00113-1Get rights and content

Abstract

Thorn-shaped astrocytes (TSA) are glial fibrillary tangles that contain abnormally phosphorylated and aggregated microtubule-associated tau protein. The present study examines the prevalence of TSA in the human medial temporal lobe of 100 autopsy brains aged 42–97 years (mean age: 65 years). Serial brain sections were cut at 100 μm and stained using phosphorylation-dependent anti-tau antibodies (AT8, PHF-1, TG3, Alz-50) and silver staining methods for neurofibrillary changes and β-amyloid deposits. TSA preferentially were distributed in periventricular, subependymal, and subpial areas of the mediobasal temporal lobe (MTL). Double-labeling with AT8 and anti-GFAP antibodies demonstrated that the abnormal tau protein was deposited in astroglial cell bodies and in proximal and distal astroglial processes. A pronounced inter-individual variation was noted in the density of AT8-positive TSA, thereby allowing distinction of mild, moderate, and severe involvement. TSA were absent in individuals younger than 60 years. A significant increase in the prevalence of TSA was noted with advancing age. In the age-range of 75–98 years TSA were found in approximately 50% of all individuals. The development of TSA was not correlated with the severity of Alzheimer-related cortical pathology. In summary, this study suggests that TSA is a distinct form of glial tau pathology that occurs with a high frequency in elderly individuals.

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.

Section snippets

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).

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