Koutarapu, Srinivas;
Ge, Junyue;
Jha, Durga;
Blennow, Kaj;
Zetterberg, Henrik;
Lashley, Tammaryn;
Michno, Wojciech;
(2022)
Correlative chemical imaging identifies amyloid peptide signatures of neuritic plaques and dystrophy in human sporadic Alzheimer's disease.
Brain Connectivity
10.1089/brain.2022.0047.
(In press).
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Abstract
OBJECTIVE: Alzheimer's disease (AD) is the most common neurodegenerative disease. The predominantly sporadic form of AD (sAD) 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 (Aβ) plaque pathology. According to the amyloid cascade hypothesis, Aβ is the critical early initiator of AD pathogenesis. Plaque pathology is very heterogeneous, where a subset of plaques, neuritic plaques, are considered most neurotoxic rendering their in depth characterization essential to understand Aβ pathogenicity. METHODS: To delineate the chemical traits specific to neuritic plaque types, we investigated senile Aβ pathology in post mortem human sporadic AD brain using advanced correlative biochemical imaging based on immunofluorescence microscopy and mass spectrometry imaging (MSI). RESULTS: Immunostaining-guided MSI identified distinct Aβ signatures of neuritic plaques characterized by increased Aβ 1-42(ox) and Aβ2-42. Moreover, correlation with a marker of dystrophy (reticulon 3, RTN3) identified key Aβ species that both delineate neuritic plaques and display association with neuritic dystrophy. CONCLUSION: Together these correlative imaging data shed light on the complex biochemical architecture of neuritic plaques and associated dystrophic neurites. These in turn are obvious targets for disease-modifying treatment strategies, as well as novel biomarkers of Aβ pathogenicity.
| Type: | Article |
|---|---|
| Title: | Correlative chemical imaging identifies amyloid peptide signatures of neuritic plaques and dystrophy in human sporadic Alzheimer's disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1089/brain.2022.0047 |
| Publisher version: | https://doi.org/10.1089/brain.2022.0047 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer's Disease, Neuroanatomy, Neurodegenerative disorders |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10155968 |
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