Morphologic features of synaptic structures associated with human cortical amyloid plaques

Abstract

BACKGROUND: Progressive and irreversible synaptic loss is a key manifestation of Alzheimer’s disease (AD) that correlates with the degree of AD-associated cognitive impairment. The study of synaptic impairment may be necessary to understand the AD development and progression. Therefore, it seems important to analyze structural and functional changes in synapses during the development of this disease. Synaptophysin, a synaptic vesicle membrane protein, is one of the most reliable and widely used synaptic markers in such studies.

AIM: The aim of this study was to investigate the morphological characteristics of synaptophysin-containing structures in the human cerebral cortex during amyloid plaque formation.

MATERIALS AND METHODS: The study used cerebral cortex samples (n = 10) from men and women between the ages of 65 and 94 years. A new and original technique for light microscopy based on immunohistochemical detection of synaptophysin and staining of amyloid plaques with Alcian Blue was used for the simultaneous detection of synapses and amyloid plaques.

RESULTS: In most amyloid plaques, abnormal synaptophysin-immunopositive structures were found, presumably representing dystrophic presynapses. These structures were characterized by large size and diffuse shape and were found exclusively in amyloid plaques. It should be mentioned that polysaccharide bodies (corpora amylacea) were detected in all samples of the cerebral cortex, characterized by a distinct spherical shape and located predominantly near the meninges, periventricularly and perivascularly. Synaptophysin-immunopositive terminals surrounding polysaccharide bodies had a typical structure and distribution density in all cases and showed no signs of abnormality.

CONCLUSIONS: In the cerebral cortex of elderly, senile, and long-lived individuals with AD, abnormal synaptophysin-containing structures form within or around amyloid plaques. Further study of these structures promises to identify new biomarkers of synaptic disorganization, including AD and early diagnostic markers for AD.

Keywords

synapses / synaptophysin / amyloid plaques / corpora amylacea / Alzheimer’s disease

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Funding

Правительство Российской ФедерацииGovernment of the Russian FederationGovernment of the Russian Federation(FGWG-2024-0015)

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