Unless otherwise noted, data are expressed as mean ±

SEM. For dendritic spine analysis, all data were obtained from at least three independent experiments or at least three individual mice. The test was considered significant when p < 0.05. For all analyses, the following apply: ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; ns, not significant p > 0.05. For clarity purpose, the color of the marker (asterisk [∗] or “ns”) refers to the corresponding condition used for statistical comparison. We would like to thank members Epigenetics inhibitor of the F.P. lab for discussions, Dr. Reuben Shaw (Salk Institute, La Jolla, CA, USA) for the AMPK constructs, Dr. Pascal Lacor (Northwestern University School of Medicine, Chicago, IL, USA) for initial advice on Aβ oligomer production, Dr. Benoit Viollet (INSERM, Institut Cochin, Paris, France) for providing AMPKα1 knockout mice, and Dr. Talal Chatila (Harvard Medical School, Boston, MA, USA) for providing CAMKK2 knockout mice. This work was partially supported by NIH RO1 AG031524 (to F.P.) and ADI Novartis

funds (to F.P.). “
“Neuronal microtubules (MTs) are biochemically TGF-beta inhibition and physiologically diverse. Multiple genes for α- and β-tubulins are expressed differentially during development and regeneration. Tubulins are also subject to posttranslational modifications, and contain a heterogeneous group of microtubule-associated proteins (MAPs) (Ludueña, 1998). next The functional consequences of such diversity are thought to be generating MTs suited for unique demands of cells. Neurons are unusually polarized, with a single long axon and multiple branching dendrites. MTs in axons may be very long (more than hundreds of microns in axons), and axonal MTs are maintained for weeks or months at considerable

distances from sites of tubulin synthesis (>1 m in some human nerves), imposing unusual constraints on neuronal MTs. Unlike MTs in nonneuronal cells, which can be highly dynamic (Desai and Mitchison, 1997), axonal MTs are more stable, allowing them to act as a structural framework for the neuron, serve as tracks for organelle transport, maintain cell shape and connections, and define functional compartments (Brady, 1993). Moreover, MTs in axons are not continuous with a perikaryal microtubule organizing center or visible nucleating structure (Yu and Baas, 1994). How can axonal MTs extend for such distances and be stable for so long, yet retain the ability to be modified in response to physiological stimuli? A simple answer would be the presence of a significant fraction of stable MTs. This stable MT fraction is important not only for cytoskeletal organization in early neuronal development (Kirkpatrick and Brady, 1994; Kirkpatrick et al.