Evidence map›Paper›PMID 42529446›Full record

ArticleJACS Au2026

Spatially Resolved Free Fatty Acid Profiling Reveals Region- and Age-Dependent Remodeling of Alzheimer's Disease Plaques.

Sona Hakhverdyan, Sofie Hansson, Pascal Kadej, Sophia B Orlovsky, Siarhei Hladkou, Birger Viirman, Anna Nilsson, Martin Lord, Stephanie M Cologna, Justin T Mohr and 3 more

Abstract read
In one paragraph

Article in JACS Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Sona HakhverdyanDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Sofie HanssonDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Pascal KadejDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Sophia B OrlovskyDepartment of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States.
Siarhei HladkouDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Birger ViirmanDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Anna NilssonDepartment of Pharmaceutical Biosciences, Spatial Mass Spectrometry, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden.
Martin LordDepartment of Pharmacy, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden.
Stephanie M ColognaDepartment of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States.ORCID https://orcid.org/0000-0002-3541-3361
Justin T MohrDepartment of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States.ORCID https://orcid.org/0000-0002-7005-3322
Stina SyvänenDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.
Per E AndrénDepartment of Pharmaceutical Biosciences, Spatial Mass Spectrometry, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden.ORCID https://orcid.org/0000-0002-4062-7743
Wojciech MichnoDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, SE-75237 Uppsala, Sweden.ORCID https://orcid.org/0000-0002-3096-3604

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Free fatty acids (FFAs) are bioactive mediators of inflammation, energy metabolism, and membrane remodeling, yet their spatial organization within the Alzheimer's disease (AD) brain and at individual amyloid-β (Aβ) plaques has remained inaccessible. We developed a novel, chemically tailored MALDI workflow that enables simultaneous, spatially resolved detection of nearly 30 FFAs alongside over 100 complex lipid species within the same tissue section. Applying this approach to a transgenic AD mouse model across brain regions and disease stages, and combining it with single-plaque microenvironment analysis (SPMA) that treats each plaque as an individual analytical object, we uncover two previously inaccessible dimensions of plaque-associated lipid biology. FFA distributions form highly structured spatial compartments reflecting regional cytoarchitecture, with distinct enrichment of saturated, monounsaturated, and polyunsaturated species across cortical layers. Within Aβ plaques, nearly 75% of detected FFAs are significantly remodeled, with reciprocal enrichment of short saturated and highly unsaturated species alongside depletion of long-chain monounsaturated FFAs. This pattern is consistent with concurrent disruption of ELOVL-mediated elongation and FADS-mediated desaturation, including opposing enrichment of pro-inflammatory arachidonic acid and pro-resolving docosahexaenoic acid. Machine learning of single-plaque profiles reveals that FFA composition alone classifies plaque age with high accuracy, demonstrating that lipid remodeling continues after Aβ peptide composition has stabilized. Together, these findings establish spatial FFA profiling as a new analytical dimension in neurodegeneration research, revealing that Aβ plaques are dynamic lipid-metabolic microenvironments that continue to remodel long after Aβ deposition has stabilized.

Indexed as

Alzheimer’s disease (AD)amyloid-β (Aβ) pathologyfree fatty acids (FFA)lipid metabolismmass spectrometry imaging (MSI)matrix-assisted laser desorption/ionization (MALDI)spatial lipidomics

Identifiers

PMID42529446
PMCPMC13417193

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.