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.

Základní údaje

Originální název

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

Autoři

KOUTARAPU, Srinivas; Junyue GE; Durga JHA; Kaj BLENNOW; Henrik ZETTERBERG; Tammaryn LASHLEY; Wojciech MICHNO a Jorg HANRIEDER

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30103 Neurosciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 2.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00133213

Organizační jednotka

Přírodovědecká fakulta

EID Scopus

Klíčová slova anglicky

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

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 25. 1. 2024 11:26, Mgr. Marie Novosadová Šípková, DiS.

Anotace

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.