While the AD filament fold excludes the R1 and R2 domain of the microtubule-binding repeat domains, and can thus incorporate both 3R and 4R isoforms in its structure, other sporadic tauopathies have filament structures that allow incorporation of only 3R (PiD) or 4R (CBD, PSP) tau isoforms (35). This evidence concerns the gene MAPT and Alzheimer disease.