Cortical connections and the pathology of Alzheimer's disease

The hypothesis that the distribution of neurodegeneration in Alzheimer's disease results from the spread of the pathology via anatomical connections is reviewed in the light of recent advances in knowledge of the connectivity of the cerebral cortex. Current understanding of cortical connections allows a more detailed examination of the distribution of pathology, particularly neurofibrillary tangles, in relation to this hypothesis. In particular, quantitative assessment of corticocortical pathways opens up the possibility of specific testing of the hypothesis. Theoretical considerations are discussed, and a predicted spread of pathology beginning in the olfactory centres of the medial temporal lobe and spreading retrogradely via known pathways is presented.