Paired helical filaments in astrocytes: electron microscopy and immunohistochemistry in a case of atypical Alzheimer's disease

Summary A 54-year-old man who had cerebellar ataxia and pseudobulbar palsy at the age of 29 years, and soon developed dementia, myoclonus and convulsions, died after about 20 years in a vegetative state. Histological examination of the extensively atrophic and devastated brain (680 g) revealed the almost total loss of cerebral cortical neurons associated with numerous -protein amyloid plaques, many extracellular tangles and a large number of hypertrophic astrocytes, and prominent amyloid angiopathy. The astrocytes were frequently immunopositive for anti-human tau antibody (anti-htau) and anti-ubiquitin antibody (anti-ubi). Double immunostaining with anti-htau and anti-glial fibrillary acidic protein (GFAP) antibody clearly demonstrated htau-positive domains within the GFAP-positive perikarya/and processes of several astrocytes. Electron microscopy of the hippocampal CA1, which was completely devoid of pyramidal neurons, revealed, in astrocytes, abnormal filaments indistinguishable from the paired helical filaments (PHFs) seen in neurons. On immunoelectron microscopy, the filaments were observed to be labeled with anti-htau and anti-ubi, exhibiting the same immunohistochemical features as neuronal PHFs. This is the first demonstration of clearly constricted and both tau- and ubiquitin-positive PHFs in astrocytes, indicating that, in some special conditions like in our case, processes similar to those that attack neurons also affect astrocytes and ultimately make the latter form PHFs.Supported in part by Grants-in-Aid for Scientific Research on Priority Areas, Nos. 01658005 and 02240104, from the Ministry of Education, Science and Culture, Japan