Posterior parahippocampal gyrus pathology in Alzheimer's disease

The posterior parahippocampal gyrus (PPHG) of the non-human primate brain has a distinct dual role in cortical neural systems. On the one hand, it is a critical link in providing the entorhinal cortex and hippocampal formation with cortical input, while on the other hand it receives output from these structures and projects widely by disseminating the medial temporal lobe output to the cortex. Layer III of TF and TH areas largely mediate the former (input) while layer V mediates the latter (output). We have examined areas TF and TH in the normal human brain and in Alzheimer's disease (AD) using pathological stains (Nissl, Thioflavin S) and phenotype specific stains non-phosphorylated neurofilament protein (SMI32) and parvalbumin (PV). Seven clinically and pathologically confirmed AD cases have been studied along with six age-compatible normal cases. Our observations reveal that neurofibrillary tangles (NFTs) heavily invest the area TF and TH neurons that form layers III and V. In both cortical areas, the large pyramids that form layer V contain a greater number of NFTs. These changes, and possibly, pyramidal cell loss, greatly alter the cytoarchitectural picture and diminish SMI32 staining patterns. Layer III of area TH loses the majority of SMI32 immunoreactivity, whereas this change is more conspicuous in layer V of area TF. PV-staining in both areas is largely unaffected. Normal cases contained no evidence of pathology or altered cytoarchitecture. These observations reveal a further disruption of memory-related temporal neural systems in AD where pathology selectively alters both the input to the hippocampal formation and its output to the cortex.