title: Reversal of long-term dendritic spine alterations in Alzheimer disease models.
abstract: Synapse loss is strongly correlated with cognitive impairment in Alzheimer's disease (AD). We have previously reported the loss of dendritic spines and the presence of dystrophic neurites in both the hippocampi of transgenic mice overexpressing amyloid precursor protein (APP) and in the human brain affected with AD. In the studies reported here we have asked whether the acute alterations in dendritic spines induced by Abeta, as well as the chronic loss of spine density seen in hAPP transgenic mice, are reversible by treatments that restore the cAMP/PKA/CREB signaling pathway or proteasome function to control levels. The results show that both rolipram and TAT-HA-Uch-L1 restore spine density to near control conditions, even in elderly mice. The results suggest that changes in dendritic structure and function that occur after Abeta elevation are reversible even after long periods of time, and that one could envision therapeutic approaches to AD based on this restoration that could work independently of therapies aimed at lowering Abeta levels in the brain.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Smith
authors.forename: Julio
authors.initials: J
authors.lastname: Pozueta
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.forename: Michael
authors.initials: M
authors.lastname: Shelanski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor