数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
Alzheimer’s disease (AD) is a major neurodegenerative disorder affecting millions of individuals worldwide.
方法
The dataset included samples from the superior temporal gyrus (STG), contributed by 244 individuals across control and pathologically defined AD cases [23].；Fixed modifications included carbamidomethylation (C, +57.0215 Da) and the isobaric tandem mass tag (TMT) label on lysine.；At the PSM level, log ratios were calculated as the average of log-transformed values across AD patients for each PSM.
核心结论
Spectra were searched with the open-search engine PIPI-C [20], which detects multiple co-occurring modifications on individual peptides [19], using the AMP-AD datasets [22] and the UNIMOD modification and substitution library [27] as input; substitution-bearing spectra were then re-scored with Comet [21], and both engines were controlled at a PSM-level FDR of 1% (Section 2.2).；After excluding PSMs attributed exclusively to TMT labeling mass shifts, about 31% of PIPI-C-identified PSMs carried a single AA substitution, and 15% harbored multiple substitutions. ‖ 结论：We detected substitutions at two GFAP positions (242 and 352) at which mutations causing Alexander disease, a rare neurodegenerative disorder, have been reported.
局限
This does not establish a translational origin: somatic variation, RNA editing and unannotated variants remain possible, and the origin of individual events cannot be assigned from MS data alone and requires orthogonal validation.；It is limited by the number of TMTpro experiments available within each institution rather than by the quality of the identifications.
对本项目的价值
★★★★☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。最大样本量约 244；设计 Meta 分析、回顾性。
全文来源
PMC JATS 全文（正文 51,266 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Profiling Amino Acid Substitutions in Proteomic Datasets of Alzheimer's Disease Reveals Biological Significance.
- 期刊与标识：Biomedicines · PMID 42940148 · DOI 10.3390/biomedicines14102342**
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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