Differential Incorporation of Tau Isoforms in Alzheimer's Disease

Abstract

There are 6 different isoforms of tau expressed in the adult human brain, and little information is available on the cellular distribution of the isoforms. Tau inclusions are found in neurons and occasionally glia in a variety of diseases. Previous studies conducted on brain homogenates suggested that tau isoforms might be differentially incorporated into inclusions. To further elucidate the complex issue of tau isoform composition in Alzheimer's disease (AD) and other neurodegenerative diseases, monoclonal antibodies that differentiate between tau containing residues encoded by exon 10 (4R tau) and tau lacking exon 10 residues (3R tau) were used in single and double labeling immunohistochemistry as well as biochemical analyses of tau isolated from AD and other neurodegenerative diseases. Immunohistochemical analysis of the hippocampus in 34 AD cases performed with these antibodies showed both 3R and 4R tau isoforms in tangles. While biochemical studies showed that both isoforms were present in insoluble tau aggregates in AD hippocampus and cortex, not all tangles appear to be labeled with the 3R and 4R tau specific monoclonal antibodies. Similar studies in progressive supranuclear palsy and Pick's disease confirmed that these diseases were characterized by incorporation of specific isoforms in fibrillar lesions, but lesions in neither disease were exclusively composed of 3R tau or 4R tau isoforms.