Various chronic neurological diseases are associated with increased expression of transforming growth factor‐beta1 (TGF‐β1) in the brain. TGF‐β1 has both neuroprotective and neurodegenerative functions, depending on conditions such as duration and the local and temporal pattern of its expression. Previous transgenic approaches did not enable control for these dynamic aspects. To overcome these limitations, we established a transgenic mouse model with inducible neuron‐specific expression of TGF‐β1 based on the tetracycline‐regulated gene expression system. TGF‐β1 expression was restricted to the brain where it was particularly pronounced in the neocortex, hippocampus and striatum. Transgene expression was highly sensitive to the presence of doxycycline and completely silenced within 6 days after doxycycline application. After long‐term expression, perivascular thioflavin‐positive depositions, formed by amyloid fibrils, developed. These depositions persisted even after prolonged silencing of the transgene, indicating an irreversible process. Similarly, strong perivascular apolipoprotein E (ApoE) depositions were found after TGF‐β1 expression and these remained despite TGF‐β1 removal. These in vivo observations suggests that the continuous presence of TGF‐β1 as intitial trigger is not necessary for the persistence and development of chronic lesions. Neuroprotective effects were observed after short‐term expression of TGF‐β1. Death of striatal neurons induced by 3‐nitropropionic acid was markedly reduced after induced TGF‐β1 expression.