Structure and function of the entorhinal cortex with special reference to neurodegenerative disease

The entorhinal cortex (EC) comprises the anterior portion of the parahippocampal gyrus (PHG) and constitutes an important part of the medial temporal lobe (MTL) of the brain. The EC is involved in a variety of brain functions including the analysis of olfactory information, various types of memory, and the final integration of sensory data before being transmitted to the hippocampus (HC) via the perforant path. Significant pathology occurs in the EC and HC in neurodegenerative disease and therefore, these regions may be involved in the development of the cognitive deficits characteristics of these disorders. Based on the severity of pathological change in the EC, neurodegenerative disorders can be divided into three groups: (1) those in which high densities of neuronal cytoplasmic inclusions (NCI) and/or extracellular protein deposits occur in the EC, e.g., Alzheimer’s disease (AD), Down’s syndrome (DS), and sporadic Creutzfeldt-Jakob disease (sCJD), (2) those with moderate densities of NCI and/or extracellular protein deposits in the EC, e.g., argyrophilic grain disease (AGD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease (PiD), neuronal intermediate filament inclusion disease (NIFID), and variant CJD (vCJD), and (3) those in which there is relatively little pathology in the EC, e.g., Parkinson’s disease dementia (PD-Dem), frontotemporal lobar degeneration with TDP-43-immunoreactive inclusions (FTLD-TDP), and multiple system atrophy (MSA). Hence, EC pathology varies significantly among disorders which could contribute to differences in the development of memory deficits among dementias. Pathological differences among disorders could reflect either differential vulnerability of the EC to specific molecular pathologies or variation in the degree of spread of pathological proteins among regions of the MTL.