Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer's and Creutzfeldt-Jakob Disease: A Micromorphological Pilot Study on 20 Brains.

Nikol Jankovska,Radoslav Matej,Tomas Olejar

doi:10.3390/ijms22042099

Nikol Jankovska, Radoslav Matej + Show 1 more

Open Access

https://doi.org/10.3390/ijms22042099

Copy DOI

Abstract

Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.

Highlights

Deposits of extracellular protein aggregates are diagnostic findings for two separate neurodegenerative diseases, i.e., Alzheimer’s (AD) and Creutzfeldt–Jakob diseases (CJD) [1,2]
Amyloid-β peptide (Aβ) is a main defining component of amyloid β-protein (Aβ) plaques observed in Alzheimer’s disease (AD) [3,4]. These extracellular deposits arise from the amyloidogenic cleavage of an integral membrane protein, called amyloid precursor protein (APP), by beta-site APP cleaving enzyme 1 (β-secretase/BACE 1), which is found on neuronal membranes [5]
We evaluated using immunohistochemistry and confocal microscopy, the micromorphology of PrPSc colocalized with Aβ in dystrophic neurites with compound plaques in the brains of patients with comorbid Alzheimer’s and Creutzfeldt–Jakob disease [21]

Summary

Introduction

Deposits of extracellular protein aggregates are diagnostic findings for two separate neurodegenerative diseases, i.e., Alzheimer’s (AD) and Creutzfeldt–Jakob diseases (CJD) [1,2]. Amyloid-β peptide (Aβ) is a main defining component of Aβ plaques ( called amyloid or senile plaques) observed in AD [3,4]. These extracellular deposits arise from the amyloidogenic cleavage of an integral membrane protein, called amyloid precursor protein (APP), by beta-site APP cleaving enzyme 1 (β-secretase/BACE 1), which is found on neuronal membranes [5]. In addition to APP and BACE 1, the physiological isoform of the prion protein (PrPC ) is found on the outer surface of neuronal membranes; it is attached to the membrane via a glycosylphosphatidylinositol (GPI) anchor [6]. Aβ plays a critical role in brain development, neuronal migration, and synaptic plasticity [7]

Methods

Results

Conclusion