BACKGROUND: P73 belongs to the p53 family of cell survival regulators with the 
corresponding locus Trp73 producing the N-terminally distinct isoforms, TAp73 
and DeltaNp73. Recently, two studies have implicated the murine Trp73 in the 
modulation in phospho-tau accumulation in aged wild type mice and in young mice 
modeling Alzheimer's disease (AD) suggesting that Trp73, particularly the 
DeltaNp73 isoform, links the accumulation of amyloid peptides to the creation of 
neurofibrillary tangles (NFTs). Here, we reevaluated tau pathologies in the same 
TgCRND8 mouse model as the previous studies.
RESULTS: Despite the use of the same animal models, our in vivo studies failed 
to demonstrate biochemical or histological evidence for misprocessing of tau in 
young compound Trp73+/- + TgCRND8 mice or in aged Trp73+/- mice analyzed at the 
ages reported previously, or older. Secondly, we analyzed an additional mouse 
model where the DeltaNp73 was specifically deleted and confirmed a lack of 
impact of the DeltaNp73 allele, either in heterozygous or homozygous form, upon 
tau pathology in aged mice. Lastly, we also examined human TP73 for single 
nucleotide polymorphisms (SNPs) and/or copy number variants in a meta-analysis 
of 10 AD genome-wide association datasets. No SNPs reached significance after 
correction for multiple testing and no duplications/deletions in TP73 were found 
in 549 cases of AD and 544 non-demented controls.
CONCLUSION: Our results fail to support P73 as a contributor to AD pathogenesis.