Molecular and anatomical studies in Alzheimer's disease

This chapter builds on the themes developed during the last 10 years of studying the neuroanatomical basis of Alzheimer's disease (AD) from a neural systems perspective. Indirect evidence suggests that Abeta deposits are a dynamic lesion, and that a subset of Abeta deposits that stain for thioflavine S (thioS) are a critical lesion in terms of effects on neurons and their processes. Parallel studies in transgenic mice point to the same conclusion. Finally, we will discuss recent studies, using a remarkable microscropy tool that we have developed -an application of multiphoton microscopy- for in vivo histology, and in vivo functional imaging in living, anesthetized transgenic mice. Resolution is well below a micrometer, and cortical depths up to approximately 300 microns beneath the skull can be imaged; the mice recover uneventfully and can be reimaged days to months later. With this new technique, we can, for the first time, study dynamic processes of A beta deposition and resolution in a living brain.