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 (356 Indie, domácí), 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: 3.400 v roce 2022
Kód RIV
RIV/00216224:14310/23:00133213
Organizační jednotka
Přírodovědecká fakulta
UT WoS
001008190800006
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 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.