Dataset Information

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

ABSTRACT: Alzheimer's disease (AD) and sporadic Creutzfeldt-Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins-amyloid ?-protein (A?) and prion protein (PrP^Sc), respectively. To investigate the potential morphological colocalization of A? and PrP^Sc 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 A? and PrP^Sc aggregates tended to be, in most cases, located separately, and "compound" plaques were relatively rare. We observed PrP^Sc plaque-like structures in the periphery of the non-compact parts of A? 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 A?/PrP^Sc co-aggregates. However, our data showed that PrP^Sc aggregation could dominate during co-aggregation with non-compact A? in the periphery of A? plaques.

SUBMITTER: Jankovska N

PROVIDER: S-EPMC7924045 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Jankovska Nikol N Olejar Tomas T Matej Radoslav R

International journal of molecular sciences 20210220 4

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 (PrP<sup>Sc</sup>), respectively. To investigate the potential morphological colocalization of Aβ and PrP<sup>Sc</sup> aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunoh ...[more]

PMID: 33672582

Similar Datasets

Project description:Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients.To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD.A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD.Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-d-aspartate (NMDA), and glycine (GlY) receptors.Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [?/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs.A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets