Pathological hallmark of Alzheimer's disease (AD) is characterized by the accumulation and aggregation of amyloid β (Aβ) peptides into extracellular plaques of the brain. Clarification of the process of how soluble Aβ starts to assemble into amyloid fibrils is an essential step in elucidating the pathogenesis of AD. In our previous study, Aβ proteoforms including full-length Aβ40 and Aβ42/43 with N- and C-terminal truncated forms were visualized in postmortem brains from AD patients with matrix-assisted laser desorption/ionization-based mass spectrometry imaging (MALDI-MSI). In this study, Aβ proteoforms were consistently visualized by an updated protocol, and uncharacterized peptides such as Aβ1-29 and Aβ10-40 in AD brains were also visualized. To decipher neurotoxic effects of Aβ in patients' brains, here we integrate liquid chromatography tandem mass spectrometry (LC-MS/MS) based shotgun proteomics with laser microdissection (LMD) excised tissue samples as well as direct tissue imaging with MALDI-MSI. With this approach, we have highlighted dynamic alterations of microtubule associating proteins (MAPs) including MAP1A, MAP1B and MAP2 as well as AD dominant proteins including APP, UCHL1, SNCA, and APOE. Of note, as lipid dysregulation has been implicated with AD pathology, we have challenged to integrate proteomics and lipid imaging for AD and control brain tissue. Spatial multi-omics is also valid to uncover molecular pathology of white matter as well as grey matter and leptomeningeal area, for example, by visualizing heme in patients' postmortem brains.

Yumiko Toyama

Takashi Nirasawa

Maho Morishima

Yuko Saito

Kazuhiro Irie

Shigeo Murayama

Masaya Ikegawa

ACTA HISTOCHEMICA ET CYTOCHEMICA

ACTA HISTOCHEMICA ET CYTOCHEMICA 是日本组织化学和细胞化学学会的官方在线期刊。它主要用于快速出版组织化学和细胞化学领域的简明原创文章。面向包含这些领域重大技术进步的方法论主题的手稿也受到欢迎。任何国家的研究人员都接受英文手稿，无论他们是否是日本组织化学和细胞化学学会的成员。手稿应该是以前未发表过且不考虑在其他地方发表的原创作品，摘要除外。与已发表或接受或正在考虑发表的论文内容基本相同的手稿将不予考虑。所有提交的论文将由适当的副主编选择的至少两名审稿人进行同行评审。接受基于科学意义、原创性和清晰性。需要时，应在3个月内提交修改稿，否则视为新投稿。主编将就接受做出所有最终决定。

Acta Histochemica et Cytochemica is the official online journal of the Japanese Society of Histochemistry and Cytochemistry, aimed at the rapid publication of original research articles in the fields of histochemistry and cytochemistry. We welcome manuscripts that address significant methodological advancements in these areas, and researchers from any country may submit manuscripts in English, regardless of their membership status with the Japanese Society of Histochemistry and Cytochemistry. All submitted manuscripts must be original works that have not been published elsewhere, excluding abstracts. Manuscripts that are substantially similar to papers that have been published, accepted, or are under consideration will not be considered. All submitted papers will undergo peer review by at least two reviewers selected by the appropriate associate editor, based on criteria including scientific significance, originality, and clarity. If revisions are necessary, authors must submit the revised manuscript within three months; otherwise, it will be treated as a new submission. The editor-in-chief will make all final decisions regarding acceptance.

《Acta Histochemica et Cytochemica》是日本组织化学和细胞化学学会的官方在线期刊，旨在快速发表组织化学和细胞化学领域的原创性研究文章。我们欢迎涉及这些领域重大技术进步的手稿，无论作者是否为日本组织化学和细胞化学学会的成员，均可提交英文稿件。所有提交的手稿必须是未曾发表过的原创作品，摘要除外。与已发表、接受或正在考虑发表的论文内容基本相同的手稿将不予考虑。所有提交的论文将由至少两名由适当副主编选择的审稿人进行同行评审，评审标准包括科学意义、原创性和清晰性。若需修改，作者应在3个月内提交修改稿，否则将视为新投稿。主编将对此做出最终决定。

Category	Quartile
生物学	4
生物学, 细胞生物学	4

Integrated Spatial Multi-Omics Study of Postmortem Brains of Alzheimer’s Disease

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
CELL BIOLOGY	4