The entorhinal cortex, which is involved in neural systems related to memory, is selectively degenerated in early
Alzheimer's disease. Here, we examined neuropathological changes in the eight entorhinal subfields in post mortem
Alzheimer's disease subjects using
Thionin and Bielschowsky stains and
parvalbumin,
calretinin and
calbindin-D28k immunohistochemistry. Both histological stains revealed the most dramatic cell loss and neurofibrillary tangle formation to be in layers II and V of the lateral, intermediate and caudal subfields. In accordance, immunohistochemical staining showed that neurons and fibres that contain
calcium-binding proteins were also more frequently altered in these subfields than in the rostromedial subfields. Detailed analysis further revealed that non-principal cells containing
parvalbumin or
calbindin-D28k showed morphological alterations early in the entorhinal pathology of
Alzheimer's disease, whereas non-principal neurons containing
calretinin were better preserved even in
Alzheimer's disease patients with severe entorhinal pathology. The degeneration of
parvalbumin-immunoreactive neurons and basket-like networks and
calbindin-positive non-principal neurons was observed mainly in layer II, where the
calretinin-positive non-principal neurons formed aggregates especially at late stages of the disease. The pyramidal-shaped neurons containing either
calretinin or
calbindin-D28k were often preserved, although morphological alterations were observed. Our findings indicate that specific subfields of the entorhinal cortex involving neurons that contain distinct
calcium-binding proteins are differentially vulnerable in
Alzheimer's disease. This could have an impact on the topographically organized inputs and outputs of the entorhinal cortex in Alzheimer's patients.