Several groups have reported a lack of phenotype in α-synuclein (α-S) transgenic mice, but it appears Lennart Mucke (122.10) has got it right. Mucke reported that inclusion bodies were obvious in PDGF promoter-driven α-S Tg mice as early as three-four months, and that these inclusions were most obvious in the higher expressing lines. Moreover, bigenic APP/α-S mice showed an increase in the number of Lewy body-like inclusions and displayed memory and learning deficits greater than mice carrying a single transgene. These observations suggest that interactions between Aα and α-S contribute significantly to dementia with Lewy bodies.—Dominic Walsh


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