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Page 221 Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expansion of the polyglutamine tract in the aminoterminal region of huntingtin. The mutant protein attenuates the action of striatal brain-derived neurotrophic factor (BDNF), which is a critical step in the pathogenesis of HD. Overexpression of BDNF in the forebrain rescues many symptoms and slows progression of the disease in mouse models of HD, apparently by redirecting subventricular zone-born neuroblasts from their normal destination, the olfactory bulb, where they develop to granule cells, to the striatum, where a fraction survives and matures. Smail et al now examined in R6/2 mice expressing a 5’ part of the human huntingtin gene in the forebrain if transgenic overexpression of BDNF in the olfactory bulb enhanced survival of subventricular zone-derived immature granule cells within their normal target structure. They observed at a late disease stage that survival of adult-born granule cells did not improve despite a slight decline in apoptotic cell death. Moreover, in the granule cell layer volume and tyrosine hydroxylase expression were reduced. Such observations have not been made in prior studies with R6/2 mice at younger ages and earlier disease stages proposing that olfactory integrity and functional circuitry is progressively impaired as the disease proceeds.