From the Department of Population Genetics, Genome Institute of Singapore (Drs. Skipper, Bonnard, Kolatkar, and Liu); Department of Neurology, Singapore General Hospital (Drs. Shen, Zhao, Yuen, and E. Tan, E. Chua, K.Y. Puong); Division of Research, SingHe
Citations 2
Analysis of
LRRK2
functional domains in nondominant Parkinson disease
JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant β-amyloid precursor protein (APP), thus modulating the APP-Aβ (β-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Aβ deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Aβ influences the formation of neurofibrillary tangles. The interaction between Aβ and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.