Cerebral inoculation of human A53T α-synuclein reduces spatial memory decline and amyloid-β aggregation in APP/PS1 transgenic mice of Alzheimer's disease.
Analogous to a successful strategy for the production of transgenic animal models for Alzheimer's disease we generated mice expressing wildtype and the A53T mutant of human alphaSN in the nervous system under control of mouse Thy1 regulatory sequences.
One of the mutant forms of alpha-synuclein (A53T) fibrillizes more rapidly in vitro than does the wild-type protein, suggesting that a correlation may exist between the rate of in vitro fibrillization and/or oligomerization and the progression of PD, analogous to the relationship between Abeta fibrillization in vitro and familial AD.
Exploration of the possibility that the same mutation of the alpha-synuclein gene as that in familial PD (Ala53Thr) may also confer susceptibility to sporadic PD, DLB, and AD revealed the mutation in none of the samples of 329 cases and 230 controls examined, suggesting that this mutation is not involved in these neurological diseases.