{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:41:23Z","timestamp":1791582083016,"version":"4.3.4"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Disruption of myelin in Alzheimer\u2019s disease has been observed by various approaches including histology, proteomics, and white matter hyperintensities in T2 FLAIR images. Since lipids are essential myelin components, we aimed to monitor N-acylphosphatidylserines (NAPSs), unique brain lipids that are altered by neuronal stress. NAPS 52:1 (PS 36:1-N16:0) was the dominant NAPS in both gray and white matter. Relative levels of NAPS 52:1 were 2.5 times higher in the periventricular white matter (PVWM) than in the hippocampus and were reduced to approximately 50% of control in both brain regions in subjects with late-onset Alzheimer\u2019s disease (LOAD). To monitor potential alterations in metabolic precursors of NAPS 52:1, we also measured the following: (1) phosphatidylcholine (PC) 36:1, which can undergo base exchange with N-acylserine (NASer) 16:0 to form NAPS 52:1; (2) phosphatidylserine (PS) 36:1, which can undergo N-acylation with palmitic acid (FA 16:0); and (3) diacylglycerol 36:1, which can be a precursor for both PC 36:1 and PS 36:1. These analyses found that only the relative levels of PS 36:1 were decreased and only in the PVWM. Next, we evaluated NASer 16:0, which can be released from NAPS 52:1 by phospholipase D. This is an N-acyl amino acid with neuroprotective properties. NASer 16:0 was found to be present at trace levels and could only be reliably monitored in the PVWM in which relative levels were decreased in LOAD subjects. In summary, reductions in NAPSs and NASer in the PVWM are lipid biomarkers of disruptions in myelin in LOAD. These data, in conjunction with our previous report of decrements in the levels of neocortical ether-PS in LOAD, suggest that these combined alterations in serine glycerophospholipid metabolism may contribute to neuronal dysfunction in dementia.<\/jats:p>","DOI":"10.3390\/life16010022","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:57:18Z","timestamp":1766487438000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["White Matter N-Acylphosphatidylserines (NAPSs) and Myelin Dysfunction in Late-Onset Alzheimer\u2019s Disease (LOAD): A Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-9936","authenticated-orcid":false,"given":"Paul L.","family":"Wood","sequence":"first","affiliation":[{"name":"Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy., Harrogate, TN 37752, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika K.","family":"Lagos","sequence":"additional","affiliation":[{"name":"Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy., Harrogate, TN 37752, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis R.","family":"Kastigar","sequence":"additional","affiliation":[{"name":"Metabolomics Unit, College of Veterinary Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy., Harrogate, TN 37752, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1212\/01.wnl.0000249119.95747.1f","article-title":"Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD","volume":"67","author":"Yoshita","year":"2006","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/jgs.15149","article-title":"Periventricular White Matter Hyperintensities and Functional Decline","volume":"66","author":"Dhamoon","year":"2018","journal-title":"J. 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