# White Matter N-Acylphosphatidylserines (NAPSs) and Myelin Dysfunction in Late-Onset Alzheimer’s Disease (LOAD): A Pilot Study

## TL;DR

This study identifies specific lipid changes in the brain's white matter that may indicate myelin dysfunction in late-onset Alzheimer's disease.

## Contribution

The study introduces NAPSs and NASer as novel lipid biomarkers for myelin disruption in late-onset Alzheimer’s disease.

## Key findings

- NAPS 52:1 levels were reduced by 50% in LOAD subjects in both gray and white matter.
- PS 36:1 levels were decreased only in the periventricular white matter of LOAD subjects.
- NASer 16:0 levels were trace and decreased in LOAD subjects in the periventricular white matter.

## Abstract

Disruption of myelin in Alzheimer’s 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’s 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.