Axonal tract tracing for delineating interacting brain regions: implications for Alzheimer's disease-associated memory.

We are studying the projections from the entorhinal cortex to the hippocampal formation in the mouse. The dentate gyrus is innervated by the lateral entorhinal cortex (lateral perforant path) and medial entorhinal cortex (medial perforant path). The entorhinal cortex also projects to hippocampal areas CA3 and CA1, and to the subiculum. In young transgenic Alzheimer's disease mouse models (before amyloid-ß pathology), the connections are not different from normal mice. In Alzheimer's disease mice with pathology, two changes occur: first, dystrophic axon endings appear near amyloid-ß plaques, and second, there are sparse aberrant axon terminations not in the appropriate area or lamina of the hippocampus. Furthermore, MRI-diffusion tensor imaging analysis indicates a decrease in the quality of the white matter tracts connecting the hippocampus to the brain; in other words, the fimbria/fornix and perforant path. Similar changes in white matter integrity have been found in Alzheimer's disease patients and could potentially be used as early indicators of disease onset.