Orbitofrontal cortex pathology in Alzheimer's disease.

The orbitofrontal cortex has been examined in Alzheimer's disease (AD) from the viewpoint of neurofibrillary tangle (NFT) pathology, its laminar distribution and topography. NFT pathology in the orbitofrontal cortex is extensive in AD. In cases with extensive cortical pathology, NFTs extend from the pole of the frontal lobe to the orbitoinsular junction. In lesser affected cases, the anterior granular part of the orbital cortex is less invested by NFTs. Layers III and V contain the greatest density of NFTs and these are most dense in the dysgranular areas, posterior to the transverse orbital sulcus. Posterior and medial orbitofrontal areas, forming area 13 and the posterior tip of the paraolfactory gyrus, are the most severely damaged, as are the smaller agranular fields that surround the olfactory tract and cortex. The widespread orbitofrontal damage in AD affecting projection neurons suggests that this pathology may contribute heavily to the many non-memory-related behavior changes observed in this disorder.