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@article{2365520,
author = {Koutarapu, Srinivas and Ge, Junyue and Jha, Durga and Blennow, Kaj and Zetterberg, Henrik and Lashley, Tammaryn and Michno, Wojciech and Hanrieder, Jorg},
article_number = {5},
doi = {http://dx.doi.org/10.1089/brain.2022.0047},
keywords = {Alzheimer's disease; beta-amyloid; cored plaques; dystrophic neuritis; matrix-assisted laser; desorption ionization mass spectrometry imaging; neuritic plaques},
language = {eng},
issn = {2158-0014},
journal = {Brain Connectivity},
title = {Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease},
url = {https://www.liebertpub.com/doi/10.1089/brain.2022.0047},
volume = {13},
year = {2023}
}
TY - JOUR
ID - 2365520
AU - Koutarapu, Srinivas - Ge, Junyue - Jha, Durga - Blennow, Kaj - Zetterberg, Henrik - Lashley, Tammaryn - Michno, Wojciech - Hanrieder, Jorg
PY - 2023
TI - Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease
JF - Brain Connectivity
VL - 13
IS - 5
SP - 297-306
EP - 297-306
PB - Mary Ann Liebert Inc.
SN - 21580014
KW - Alzheimer's disease
KW - beta-amyloid
KW - cored plaques
KW - dystrophic neuritis
KW - matrix-assisted laser
KW - desorption ionization mass spectrometry imaging
KW - neuritic plaques
UR - https://www.liebertpub.com/doi/10.1089/brain.2022.0047
N2 - 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.
ER -
KOUTARAPU, Srinivas, Junyue GE, Durga JHA, Kaj BLENNOW, Henrik ZETTERBERG, Tammaryn LASHLEY, Wojciech MICHNO and Jorg HANRIEDER. Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease. \textit{Brain Connectivity}. Mary Ann Liebert Inc., 2023, vol.~13, No~5, p.~297-306. ISSN~2158-0014. Available from: https://dx.doi.org/10.1089/brain.2022.0047.
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