Affiliations: [a] Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 526, Bronx, NY 10461, USA | [b] Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, WC1N 1PJ London, UK | [c] Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA | [d] Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 526, Bronx, NY 10461, USA
Correspondence:
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Corresponding author: Dr. Peter Davies, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Tel.: +1 718 430 3083; E-mail: [email protected].
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.
Keywords: Alzheimer's disease, neurofibrillary pathology, Pick's disease, progressive supranuclear palsy, tau, 3R tau isoforms, 4R tau isoforms
