Involvement of A1 receptors has also been observed in APP processing and tau phosphorylation in vitro, and the presence of A1 receptors in degenerating neurons with neurofibrillary tangles and Aβ-amyloid plaques in the hippocampus and frontal cortex suggest that these receptors may play a role in the pathogenesis of AD (Angulo et al., 2003). Here, MAPT is linked to Alzheimer disease.