PT - JOURNAL ARTICLE AU - Martin Fuhrmann AU - Gerda Mitteregger AU - Hans Kretzschmar AU - Jochen Herms TI - Dendritic Pathology in Prion Disease Starts at the Synaptic Spine AID - 10.1523/JNEUROSCI.5062-06.2007 DP - 2007 Jun 06 TA - The Journal of Neuroscience PG - 6224--6233 VI - 27 IP - 23 4099 - http://www.jneurosci.org/content/27/23/6224.short 4100 - http://www.jneurosci.org/content/27/23/6224.full SO - J. Neurosci.2007 Jun 06; 27 AB - Spine loss represents a common hallmark of neurodegenerative diseases. However, little is known about the underlying mechanisms, especially the relationship between spine elimination and neuritic destruction. We imaged cortical dendrites throughout a neurodegenerative disease using scrapie in mice as a model. Two-photon in vivo imaging over 2 months revealed a linear decrease of spine density. Interestingly, only persistent spines (lifetime ≥8 d) disappeared, whereas the density of transient spines (lifetime ≤4 d) was unaffected. Before spine loss, dendritic varicosities emerged preferentially at sites where spines protrude from the dendrite. These results implicate that the location where the spine protrudes from the dendrite may be particularly vulnerable and that dendritic varicosities may actually cause spine loss.