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Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry

Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer’s disease (AD). The Aβ peptides are composed of about 40 amino acids and are generated from amyloid precursor proteins (APP), by β- and γ-secretases. The distribution of individual Aβ peptides in the brains of age...

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Autores principales: Kakuda, Nobuto, Miyasaka, Tomohiro, Iwasaki, Noriyuki, Nirasawa, Takashi, Wada-Kakuda, Satoko, Takahashi-Fujigasaki, Junko, Murayama, Shigeo, Ihara, Yasuo, Ikegawa, Masaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641992/
https://www.ncbi.nlm.nih.gov/pubmed/29037261
http://dx.doi.org/10.1186/s40478-017-0477-x
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author Kakuda, Nobuto
Miyasaka, Tomohiro
Iwasaki, Noriyuki
Nirasawa, Takashi
Wada-Kakuda, Satoko
Takahashi-Fujigasaki, Junko
Murayama, Shigeo
Ihara, Yasuo
Ikegawa, Masaya
author_facet Kakuda, Nobuto
Miyasaka, Tomohiro
Iwasaki, Noriyuki
Nirasawa, Takashi
Wada-Kakuda, Satoko
Takahashi-Fujigasaki, Junko
Murayama, Shigeo
Ihara, Yasuo
Ikegawa, Masaya
author_sort Kakuda, Nobuto
collection PubMed
description Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer’s disease (AD). The Aβ peptides are composed of about 40 amino acids and are generated from amyloid precursor proteins (APP), by β- and γ-secretases. The distribution of individual Aβ peptides in the brains of aged people, and those suffering from AD and cerebral amyloid angiopathy (CAA), is not fully characterized. We employed the matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) to illustrate the spatial distribution of a broad range of Aβ species in human autopsied brains. With technical advancements such as formic acid pretreatment of frozen autopsied brain samples, we have: i) demonstrated that Aβ1–42 and Aβ1–43 were selectively deposited in senile plaques while full-length Aβ peptides such as Aβ1–36, 1–37, 1–38, 1–39, 1–40, and Aβ1–41 were deposited in leptomeningeal blood vessels. ii) Visualized distinct depositions of N-terminal truncated Aβ40 and Aβ42, including pyroglutamate modified at Glu-3 (N3pE), only with IMS for the first time. iii) Demonstrated that one single amino acid alteration at the C-terminus between Aβ1–42 and Aβ1–41 results in profound changes in their distribution pattern. In vitro, this can be attributed to the difference in the self-aggregation ability amongst Aβ1–40, Aβ1–41, and Aβ1–42. These observations were further confirmed with immunohistochemistry (IHC), using the newly developed anti-Aβ1–41 antibody. Here, distinct depositions of truncated and/or modified C- and N-terminal fragments of Aβs in AD and CAA brains with MALDI-IMS were visualized in a spacio-temporal specific manner. Specifically, Aβ1–41 was detected both with MALDI-IMS and IHC suggesting that a single amino acid alteration at the C-terminus of Aβ results in drastic distribution changes. These results suggest that MALDI-IMS could be used as a standard approach in combination with clinical, genetic, and pathological observations in understanding the pathology of AD and CAA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-017-0477-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-56419922017-10-18 Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry Kakuda, Nobuto Miyasaka, Tomohiro Iwasaki, Noriyuki Nirasawa, Takashi Wada-Kakuda, Satoko Takahashi-Fujigasaki, Junko Murayama, Shigeo Ihara, Yasuo Ikegawa, Masaya Acta Neuropathol Commun Research Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer’s disease (AD). The Aβ peptides are composed of about 40 amino acids and are generated from amyloid precursor proteins (APP), by β- and γ-secretases. The distribution of individual Aβ peptides in the brains of aged people, and those suffering from AD and cerebral amyloid angiopathy (CAA), is not fully characterized. We employed the matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) to illustrate the spatial distribution of a broad range of Aβ species in human autopsied brains. With technical advancements such as formic acid pretreatment of frozen autopsied brain samples, we have: i) demonstrated that Aβ1–42 and Aβ1–43 were selectively deposited in senile plaques while full-length Aβ peptides such as Aβ1–36, 1–37, 1–38, 1–39, 1–40, and Aβ1–41 were deposited in leptomeningeal blood vessels. ii) Visualized distinct depositions of N-terminal truncated Aβ40 and Aβ42, including pyroglutamate modified at Glu-3 (N3pE), only with IMS for the first time. iii) Demonstrated that one single amino acid alteration at the C-terminus between Aβ1–42 and Aβ1–41 results in profound changes in their distribution pattern. In vitro, this can be attributed to the difference in the self-aggregation ability amongst Aβ1–40, Aβ1–41, and Aβ1–42. These observations were further confirmed with immunohistochemistry (IHC), using the newly developed anti-Aβ1–41 antibody. Here, distinct depositions of truncated and/or modified C- and N-terminal fragments of Aβs in AD and CAA brains with MALDI-IMS were visualized in a spacio-temporal specific manner. Specifically, Aβ1–41 was detected both with MALDI-IMS and IHC suggesting that a single amino acid alteration at the C-terminus of Aβ results in drastic distribution changes. These results suggest that MALDI-IMS could be used as a standard approach in combination with clinical, genetic, and pathological observations in understanding the pathology of AD and CAA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-017-0477-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-16 /pmc/articles/PMC5641992/ /pubmed/29037261 http://dx.doi.org/10.1186/s40478-017-0477-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kakuda, Nobuto
Miyasaka, Tomohiro
Iwasaki, Noriyuki
Nirasawa, Takashi
Wada-Kakuda, Satoko
Takahashi-Fujigasaki, Junko
Murayama, Shigeo
Ihara, Yasuo
Ikegawa, Masaya
Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title_full Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title_fullStr Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title_full_unstemmed Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title_short Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
title_sort distinct deposition of amyloid-β species in brains with alzheimer’s disease pathology visualized with maldi imaging mass spectrometry
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641992/
https://www.ncbi.nlm.nih.gov/pubmed/29037261
http://dx.doi.org/10.1186/s40478-017-0477-x
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