Scholarlink

<p>Investigating the relationship of circulating lipidome profiles with cross-sectional and longitudinal changes of central Alzheimer’s disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD pathophysiology. In this study, we quantified a total of 749 plasma lipid species at baseline using liquid chromatography–mass spectrometry and performed cross-sectional and longitudinal association analysis of plasma lipidome profiles with longitudinal A/T/N biomarkers for AD in the Alzheimer’s Disease Neuroimaging Initiative cohort (N = 1395). We identified several lipid species, classes, and network modules of correlated lipids that were significantly associated with cross-sectional and longitudinal changes of A/T/N biomarkers. Notably, we identified lysoalkylphosphatidylcholine (LPC(O)) as associated with cross-sectional “A/N” biomarkers at the lipid species, class, and module levels. Also, Phosphatidylethanolamine (PE) ethers were associated with A/T/N biomarkers in the species level and with “N” biomarkers in the class and module levels. G<sub>M3</sub> ganglioside showed association with cross-sectional and longitudinal changes of “N” biomarkers at the species and class levels. Furthermore, 20 lipid species, out of all 57 species identified as associated with “less severe” AD biomarkers, contained docosahexaenoic acid (DHA), indicating that the previously reported beneficial effects of DHA on AD were significant at the central biomarker level. In conclusion, our approach linking peripheral metabolic changes with brain metabolic, structural, and functional states strengthens evidence from previous studies that were performed using only clinical AD diagnosis. Importantly, our study also enabled identification of novel lipids that play potential roles in progression of AD pathophysiology, suggesting dysregulation of lipid metabolic pathways as precursors to AD development and progression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Circulating lipids are related to longitudinal changes of ATN biomarkers for Alzheimer’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月16日

查看全文
  • Jun Pyo Kim,
  • Kwangsik Nho,
  • Tingting Wang,
  • Kevin Huynh,
  • Matthias Arnold,
  • Shannon L. Risacher,
  • Paula J. Bice,
  • Xianlin Han,
  • Bruce S. Kristal,
  • Colette Blach,
  • Rebecca Baillie,
  • Gabi Kastenmüller,
  • Peter J. Meikle,
  • Andrew J. Saykin,
  • Rima Kaddurah-Daouk,
  • Michael Weiner,
  • Paul Aisen,
  • Ronald Petersen,
  • Clifford R. Jack Jr,
  • William Jagust,
  • Susan Landau,
  • Monica Rivera-Mindt,
  • Ozioma Okonkwo,
  • Leslie M. Shaw,
  • Edward B. Lee,
  • Arthur W. Toga,
  • Laurel Beckett,
  • Danielle Harvey,
  • Robert C. Green,
  • Andrew J. Saykin,
  • Kwangsik Nho,
  • Richard J. Perrin,
  • Duygu Tosun,
  • Nick C. Fox,
  • Paul Thompson,
  • Charles DeCarli,
  • Robert A. Koeppe,
  • Gil Rabinovici,
  • John Morris,
  • Nigel J. Cairns,
  • Tatiana M. Foroud,
  • Shannon L. Risacher,
  • Rima Kaddurah-Daouk,
  • Neil Buckholtz,
  • John K. Hsiao,
  • Laurie Ryan,
  • Susan Molchan,
  • Alexandra Kueider-Paisley,
  • P. Murali Doraiswamy,
  • Colette Blach,
  • Arthur Moseley,
  • Siamak Mahmoudiandehkhordi,
  • Kathleen Welsh-Balmer,
  • Brenda Plassman,
  • Andrew J. Saykin,
  • Shannon Risacher,
  • Gabi Kastenmüller,
  • Matthias Arnold,
  • Rebecca Baillie,
  • Rob Knight,
  • Pieter Dorrestein,
  • James Brewer,
  • Emeran Mayer,
  • Jennifer Labus,
  • Pierre Baldi,
  • Arpana Gupta,
  • Oliver Fiehn,
  • Dinesh Barupal,
  • Peter Meikle,
  • Sarkis Mazmanian,
  • Dan Rader,
  • Leslie Shaw,
  • Cornelia van Duijn,
  • Najaf Amin,
  • Alejo Nevado-Holgado,
  • David Bennett,
  • Ranga Krishnan,
  • Ali Keshavarzian,
  • Robin Vogt,
  • Arfan Ikram,
  • Thomas Hankemeier,
  • Ines Thiele,
  • Cory Funk,
  • Priyanka Baloni,
  • Wei Jia,
  • David Wishart,
  • Roberta Brinton,
  • Lindsay Farrer,
  • Rhoda Au,
  • Wendy Qiu,
  • Peter Würtz,
  • Therese Koal,
  • Anna Greenwood,
  • Jan Krumsiek,
  • Karsten Suhre,
  • John Newman,
  • Ivan Hernandez,
  • Tatiana Foroud,
  • Frank Sacks

摘要

Investigating the relationship of circulating lipidome profiles with cross-sectional and longitudinal changes of central Alzheimer’s disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD pathophysiology. In this study, we quantified a total of 749 plasma lipid species at baseline using liquid chromatography–mass spectrometry and performed cross-sectional and longitudinal association analysis of plasma lipidome profiles with longitudinal A/T/N biomarkers for AD in the Alzheimer’s Disease Neuroimaging Initiative cohort (N = 1395). We identified several lipid species, classes, and network modules of correlated lipids that were significantly associated with cross-sectional and longitudinal changes of A/T/N biomarkers. Notably, we identified lysoalkylphosphatidylcholine (LPC(O)) as associated with cross-sectional “A/N” biomarkers at the lipid species, class, and module levels. Also, Phosphatidylethanolamine (PE) ethers were associated with A/T/N biomarkers in the species level and with “N” biomarkers in the class and module levels. GM3 ganglioside showed association with cross-sectional and longitudinal changes of “N” biomarkers at the species and class levels. Furthermore, 20 lipid species, out of all 57 species identified as associated with “less severe” AD biomarkers, contained docosahexaenoic acid (DHA), indicating that the previously reported beneficial effects of DHA on AD were significant at the central biomarker level. In conclusion, our approach linking peripheral metabolic changes with brain metabolic, structural, and functional states strengthens evidence from previous studies that were performed using only clinical AD diagnosis. Importantly, our study also enabled identification of novel lipids that play potential roles in progression of AD pathophysiology, suggesting dysregulation of lipid metabolic pathways as precursors to AD development and progression.