Selective deposition of 4-repeat tau in cerebral infarcts

The tau deposits found in neurodegenerative diseases are classified based on their isoforms, that is, 3-repeat (3R) tau and 4-repeat (4R) tau. These isoforms are distinguishable using the antibodies RD3 and RD4, respectively, and Gallyas (Gal) and Campbell-Switzer (CS) silver staining methods, respectively. Tau is also deposited in cerebral infarcts. To characterize the tau profile in these lesions, 21 brains from autopsied patients with cerebral infarcts were analyzed using immunohistochemistry with RD3, RD4, and the anti-paired helical filament antibody AT8 and with Gal and CS staining; all of these techniques identify Alzheimer disease-type neurofibrillary tangles. Fluorescence labeling followed by silver staining in mirror-section pairs was also used to compare the staining patterns. Neurons in and around ischemic foci exhibited the 4R-tau epitope until 34 days postinfarction; argyrophilia with Gal staining persisted longer. The 4R-tau/Gal-positive neurons were negative for 3R-tau and AT8 epitopes and lacked fibrillary structures and argyrophilia by CS staining; they are, therefore, distinct from neurons with neurofibrillary tangles. Positivity for 4R tau/Gal and negativity for 3R tau/CS were also seen in astrocytes and microglia around infarcts. Although this staining profile is characteristic of degenerative processes with 4R-tau deposition, lack of AT8 immunoreactivity and of fibrillary structures in neurons, astrocytes, and microglia indicates that selective 4R-tau deposition represents a stage without tau phosphorylation or fibril formation in cerebral infarcts.