J 2023

Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease

KOUTARAPU, Srinivas, Junyue GE, Durga JHA, Kaj BLENNOW, Henrik ZETTERBERG et. al.

Basic information

Original name

Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease

Authors

KOUTARAPU, Srinivas, Junyue GE, Durga JHA (356 India, belonging to the institution), Kaj BLENNOW, Henrik ZETTERBERG, Tammaryn LASHLEY, Wojciech MICHNO and Jorg HANRIEDER

Edition

Brain Connectivity, Mary Ann Liebert Inc. 2023, 2158-0014

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.400 in 2022

RIV identification code

RIV/00216224:14310/23:00133213

Organization unit

Faculty of Science

UT WoS

001008190800006

Keywords in English

Alzheimer's disease; beta-amyloid; cored plaques; dystrophic neuritis; matrix-assisted laser; desorption ionization mass spectrometry imaging; neuritic plaques

Tags

Tags

International impact, Reviewed
Změněno: 25/1/2024 11:26, Mgr. Marie Šípková, DiS.

Abstract

V originále

Objective: Alzheimer's disease (AD) is the most common neurodegenerative disease. The predominantly sporadic form of AD is age-related, but the underlying pathogenic mechanisms remain not fully understood. Current efforts to combat the disease focus on the main pathological hallmarks, in particular beta-amyloid (A beta) plaque pathology. According to the amyloid cascade hypothesis, A beta is the critical early initiator of AD pathogenesis. Plaque pathology is very heterogeneous, where a subset of plaques, neuritic plaques (NPs), are considered most neurotoxic rendering their in-depth characterization essential to understand A beta pathogenicity.Methods: To delineate the chemical traits specific to NP types, we investigated senile A beta pathology in the postmortem, human sporadic AD brain using advanced correlative biochemical imaging based on immunofluorescence (IF) microscopy and mass spectrometry imaging (MSI).Results: Immunostaining-guided MSI identified distinct A beta signatures of NPs characterized by increased A beta 1-42(ox) and A beta 2-42. Moreover, correlation with a marker of dystrophy (reticulon 3 [RTN3]) identified key A beta species that both delineate NPs and display association with neuritic dystrophy.Conclusion: Together, these correlative imaging data shed light on the complex biochemical architecture of NPs and associated dystrophic neurites. These in turn are obvious targets for disease-modifying treatment strategies, as well as novel biomarkers of A beta pathogenicity.