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In the CNS, SLC13A5 is described to be expressed predominantly in neurons. Cytosolic citrate levels rely on citrate generated in mitochondria and imported from other CNS cells, regulating intermediary metabolism and supplying acetyl-CoA for lipid synthesis and histone acetylation. Despite evidence for NaCT\u2019s role in neurometabolic homeostasis, its transcriptional behavior across Alzheimer\u2019s disease (AD) progression and across astrocyte subtypes remains uncharacterized at single-cell resolution. We analyzed single-nucleus RNA sequencing data from 1,378,211 nuclei across 84 donors in the Seattle Alzheimer\u2019s Disease Brain Cell Atlas (SEA-AD) Middle Temporal Gyrus dataset to profile SLC13A5 and seven citrate metabolism genes across a continuous AD pseudoprogression score. SLC13A5 expression was restricted to astrocytes (\u223c20% prevalence) and concentrated in the Astro 2 supertype (24.0%), a homeostatic subtype characterized by low C3 (1.6%) and CD44 (5.5%), which expanded with pseudoprogression (Spearman rho = +0.345, FDR &lt; 0.001). The A1-reactive Astro 3 supertype, where SLC13A5 prevalence was 0.87%, declined concordantly (rho = -0.393). Opposing compositional and transcriptional forces produced apparent stability in overall SLC13A5 prevalence. SLC13A3 and ACO1 showed progressive donor-level declines correlating with Braak stage and Thal phase (rho range: -0.307 to -0.349, FDR &lt; 0.01). APOE4 carriers exhibited lower SLC13A5 prevalence specifically within Astro 2 nuclei (median 17.6% vs. 25.9%; Wilcoxon p = 0.025), though this association did not survive multivariate regression. No difference in Astro 2 SLC13A5 expression was detected between cognitively resilient and expected-AD donors with equivalent high Braak burden (p = 0.888). Contrary to the prevailing description of NaCT as a neuronal transporter, SLC13A5 expression in the SEA-AD MTG dataset is restricted to astrocytes, concentrated in the homeostatic Astro 2 subtype, and maintained as this subtype expands with advancing AD pathology. Supertype-resolved SLC13A5 and SLC13A3 expression provide more informative readouts of astrocytic metabolic state than bulk measurements.<\/jats:p>","DOI":"10.64898\/2026.06.05.730472","type":"posted-content","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:00:20Z","timestamp":1780930820000},"source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte subtype-specific expression of the sodium-coupled citrate transporter SLC13A5 and citrate metabolism genes across Alzheimer\u2019s disease pseudoprogression: a single-nucleus RNA sequencing analysis of the human middle temporal gyrus"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-4952","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Fernanda Schuck","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Erros Inatos do Metabolismo, Programa de Bioqu\u00edmica e Biof\u00edsica Celular, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-8842","authenticated-orcid":false,"given":"Gustavo da","family":"Costa Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Erros Inatos do Metabolismo, Programa de Bioqu\u00edmica e Biof\u00edsica Celular, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1584-9157","authenticated-orcid":false,"given":"H\u00e9rcules","family":"Rezende Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inform\u00e1tica em Sa\u00fade (LabInfoS), Departamento de Ci\u00eancias M\u00e9dicas Integradas, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade do Estado do Rio de Janeiro, Cabo Frio 28905-320, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061101150991000_2026.06.05.730472v1.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207072200"},{"key":"2026061101150991000_2026.06.05.730472v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164097"},{"key":"2026061101150991000_2026.06.05.730472v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.06.006"},{"key":"2026061101150991000_2026.06.05.730472v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv263"},{"key":"2026061101150991000_2026.06.05.730472v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5499.2137"},{"key":"2026061101150991000_2026.06.05.730472v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.06.009"},{"key":"2026061101150991000_2026.06.05.730472v1.7","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2016"},{"key":"2026061101150991000_2026.06.05.730472v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0619-8"},{"key":"2026061101150991000_2026.06.05.730472v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"2026061101150991000_2026.06.05.730472v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0624-8"},{"key":"2026061101150991000_2026.06.05.730472v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"2026061101150991000_2026.06.05.730472v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00783-4"},{"key":"2026061101150991000_2026.06.05.730472v1.13","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci16020163"},{"key":"2026061101150991000_2026.06.05.730472v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01774-5"},{"key":"2026061101150991000_2026.06.05.730472v1.15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2026061101150991000_2026.06.05.730472v1.16","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.58.12.1791"},{"key":"2026061101150991000_2026.06.05.730472v1.17","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.41.4.479"},{"key":"2026061101150991000_2026.06.05.730472v1.18","unstructured":"Fischer, B. ; Smith, M. ; Pau, G. rhdf5: R Interface to HDF5; R package version 2.54.1, 2025. 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