Contrary to these findings, a recent study showed that continuous PGC-1α overexpression was cytotoxic to dopaminergic neurons in vivo[106,107]; (v) finally, by products of macromolecular oxidation, such as 4-hydroxynonenal (4-HNE), which is produced by lipid peroxidation in cells, may facilitate the self-assembly of tau protein into fibrillar polymers similar to those found in paired helical filaments (PHF), present in the brain of AD patients. Here, MAPT is linked to Alzheimer disease.