Elsevier

Neuroscience

Volume 92, Issue 2, May 1999, Pages 515-532
Neuroscience

Subfield- and layer-specific changes in parvalbumin, calretinin and calbindin-D28k immunoreactivity in the entorhinal cortex in Alzheimer's disease

https://doi.org/10.1016/S0306-4522(99)00047-0Get rights and content

Abstract

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.

Section snippets

Subjects and diagnosis of Alzheimer's disease

A total of 20 brains (14 from AD patients and six from control subjects) were used for the histological analyses. Age, sex, AD duration, mini-mental status (MMS), cause of death and post mortem delay are shown for each subject in Table 1, along with histopathological diagnoses using CERAD (the Consortium to Establish a Registry for Alzheimer's disease) criteria.44 The study was approved by the local Ethics Committee and all autopsies were performed at Kuopio University Hospital.

All AD patients

Histological analyses

The cytoarchitectonic characteristics of the eight entorhinal subfields have been previously described in detail on Thionin-stained sections by Insausti et al.33 In addition to the Thionin staining, we used the Bielschowsky stain to compare the extent of entorhinal degeneration between age-matched controls and AD cases. In only two of the control cases, occasional NFTs were observed in layer II of the lateral rostral (ELr), intermediate (EI), lateral caudal (ELc), caudal (EC) and caudal

Discussion

This is the first study to characterize in detail the AD pathology that occurs in the eight entorhinal subfields. Using two histological and three immunohistochemical stainings, we show that neurons in the entorhinal cortex are differentially vulnerable in AD in a subfield-, layer- and cell-specific manner.

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