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

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MARC

Koutarapu, SrinivasGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry (author)

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

Article/chapterEnglish2023

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2022-10-07
Mary Ann Liebert Inc,2023

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LIBRIS-ID:oai:gup.ub.gu.se/322141
https://gup.ub.gu.se/publication/322141URI
https://doi.org/10.1089/brain.2022.0047DOI

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Language:English

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Subject category:art swepub-publicationtype

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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 (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 (NPs), are considered most neurotoxic rendering their in-depth characterization essential to understand Aβ pathogenicity. Methods: To delineate the chemical traits specific to NP types, we investigated senile Aβ 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 Aβ signatures of NPs characterized by increased Aβ1-42(ox) and Aβ2-42. Moreover, correlation with a marker of dystrophy (reticulon 3 [RTN3]) identified key Aβ 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 Aβ pathogenicity.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Alzheimer's disease
beta-amyloid
cored plaques
dystrophic neuritis
matrix-assisted laser/desorption ionization mass spectrometry imaging
neuritic plaques

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Ge, Junyue,1993Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xgejul (author)
Jha, DurgaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Lashley, Tammaryn (author)
Michno, WojciechGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry (author)
Hanrieder, Jörg,1980Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xhanrj (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

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In:Brain connectivity: Mary Ann Liebert Inc15:5, s. 297-3062158-00142158-0022

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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