The hallmarks of AD are neurofibrillary tangles, intraneuronal lesions composed of aggregated hyperphosphorylated tau, and amyloid deposition, composed of aggregated Aβ [For review see (Goedert et al., 1991)]. These lesions are evident in and around vulnerable neurons in specific brain areas. The parahippocampal regions are the earliest to be affected [Braak stages I and II,(Braak and Braak, 1985; Braak and Braak, 1996)]. In particular, the entorhino-hippocampal circuit exhibits an early and significant neuropathology. Progressive neuropathology in this area correlates significantly with Braak stages, hippocampal content of abnormally phosphorylated tau (PHF-τ) and degree of dementia as defined by the clinical dementia rating (CDR) scale (Thal et al., 2000). The first morphological and cytoskeletal lesions are in pre-α cells (layer II) of the transentorhinal and entorhinal region that projects to the outer molecular layer of the dentate gyrus (Braak AD stage I). Abnormally phosphorylated tau protein is found in the neuropil of the CA1-subiculum region, followed by the stratum radiatum and stratum oriens, correlating with Braak stage II. In the Braak stages IV and V, the stratum radiatum is fully affected, and
