Fig. 1. Schematic diagram showing the organization of the six predominant isoforms of tau found in adult human brain. The number of amino acids (# aa) in each isoform is indicated at the right. The six isoforms are generated by splicing in or out exons 2 and 3 (E2 and E3) in the N-terminal region and exon 10 (E10) in the C-terminal region. The splicing in or out exon 10 results in a tau form with or without the second microtubule-binding repeat (R2), to yield isoforms with four or three microtubule-binding domains, respectively (Goedert et al., 1989). In fetal brain, only the shortest isoform of tau (352 amino acids) is present (Kosik et al., 1989). The proline-rich region is extensively phosphorylated in tau from Alzheimer's disease brain (reviewed by Johnson and Jenkins, 1999). The function of the N-terminal acidic region has not been clearly defined, although it might be involved in regulating the interaction of tau with the plasma membrane (Brandt et al., 1995).