Subfield- and layer-specific changes in parvalbumin, calretinin and calbindin-D28K immunoreactivity in the entorhinal cortex in Alzheimer's disease

The entorhinal cortex, which is involved in neural systems related to memor y, is selectively degenerated in early Alzheimer's disease. Here, we examin ed neuropathological changes in the right entorhinal subfields in post mort em Alzheimer's disease subjects using Thionin and Bielschowsky stains and p arvalbumin, calretinin and calbindin-D28k immunohistochemistry. Both histol ogical stains revealed the most dramatic cell loss and neurofibrillary tang le formation to be in layers II and V of the lateral, intermediate and caud al subfields. In accordance, immunohistochemical staining showed that neuro ns and fibres that contain calcium-binding proteins were also more frequent ly altered in these subfields than in the rostromedial subfields. Detailed analysis further revealed that non-principal cells containing parvalbumin o r calbindin-D28k showed morphological alterations early in the entorhinal p athology of Alzheimer's disease, whereas non-principal neurons containing c alretinin were better presented even in Alzheimer's disease patients with s evere entorhinal pathology. The degeneration of parvalbumin-immunoreactive neurons and basket-like networks and calbindin-positive non-principal neuro ns was observed mainly in layer II, where the calretinin-positive non-princ ipal neurons formed aggregates especially at late stages of the disease. Th e pyramidal-shaped neurons containing either calretinin or calbindin-D28K w ere often preserved, although morphological alterations were observed. Our findings indicate that specific subfields of the entorhinal cortex involvin g neurons that contain distinct calcium-binding proteins are differentially vulnerable in Alzheimer's disease. This could have an impact on the topogr aphically organized inputs and outputs of the entorhinal cortex in Alzheime r's patients. (C) 1999 IBRO. Published by Elsevier Science Ltd.