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Andy Qi"],"technology_type":["Mass Spectrometry","Data-independent acquisition","Bottom-up proteomics"],"software":[""],"submitter_keywords":["Apoe; astrocytes","Lipid proteomics","Apoe","astrocytes"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD067161"],"tissue":["Cell Culture"],"sample_protocol":["For each sample, digested peptides were analyzed using an UltiMate 3000 nano-HPLC system (Thermo Fisher Scientific) coupled with an Orbitrap Eclipse mass spectrometer (Thermo Fisher Scientific). The peptides were loaded at 5 μL/min onto a trap column (75 μm × 2 cm, PepMap nanoViper C18 column, 3μm, 100 Å, Thermo Fisher Scientific) equilibrated in 2% ACN with 0.1% trifluoroacetic acid (TFA, Thermo Scientific 85183 ). The samples were loaded to trap column for 5 min and switched  in-line with  ES903A nano C18 column (75 μm × 500 mm, 2 μm, 100 Å,Thermo Scientific) using an 80-minute linear gradient of 2% - 40% phase B (5% DMSO in 0.1% formic acid, in ACN). The column temperature was maintained at 60°C and the flow rate was set to 300 nL/min. Data were acquired in data-independent acquisition (DIA) mode. The MS1 scan was set at a resolution of 120,000, with a standard AGC target, and the maximum injection time was set to auto. The MS2 scans covered a precursor mass range of 400–1000 m/z, using an isolation window of 8 m/z with 1 m/z overlap, resulting in a total of 75 windows per scan cycle. Fragmentation was performed using high-energy collisional dissociation (HCD) with a normalized collision energy of 30%. MS2 spectra were acquired at a resolution of 30,000, with a scan range of 145–1450 m/z, and the loop control was set to 3 seconds."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["We performed DIA database searches using Spectronaut (version 19, Biognosys) with the directDIA search strategy. We used the UniProt human proteome reference with reviewed genes (20,384 entries) as the library FASTA file. directDIA false discovery rate set to 1%, protein N-terminal acetylation and methionine oxidation were set as variable modifications and carbamidomethylation of cysteine residues was selected as a fixed modification."],"omics_type":["Proteomics"],"labhead":["Ying Hao"],"instrument_platform":[""],"labhead_affiliation":["Center for Alzheimer's and Related Dementias (CARD), NIA and NINDS, NIH, Bethesda, Maryland, USA."],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["andy.qi@nih.gov"],"publication":["40894647 Cuní-López C, Root JT, Hao Y, Kowal I, Blomberg N, Ghirlando R, Yang LG, Koppes-den Hertog SJ, Cookson MR, van der Kant R, Giera M, Qi YA, Narayan PS. &lt;i&gt;APOE&lt;/i&gt; genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics. bioRxiv. 2025:2025.08.19.669163 10.1101/2025.08.19.669163"],"submitter_affiliation":["Center for Alzheimer’s Disease and Related Dementias (CARD)/NIH"],"submitter_country":["United States"],"pubmed_abstract":["The lipids and proteins that comprise lipid droplets regulate several cellular functions including lipid storage, stress responses, and inflammation. Glial lipid droplets have been implicated in the pathogenesis and progression of Alzheimer's disease (AD), yet the mechanisms linking genetic risk to lipid droplet biology remain unclear. Here we examined how <i>APOE</i>, the strongest genetic modulator of late-onset AD, impacts lipid droplet composition and dynamics. We defined the lipid droplet-associated proteome and lipidome in human induced pluripotent stem cell-derived astrocytes harboring the three common <i>APOE</i> genotypes: <i>APOE2</i> (protective), <i>APOE3</i> (neutral), and <i>APOE4</i> (risk). Each <i>APOE</i> variant displays distinct lipid droplet-associated proteins and lipids. These molecular changes yield differences in lipophagy; lipid droplets in <i>APOE2</i> astrocytes undergo autophagic turnover, whereas those in <i>APOE4</i> astrocytes are resistant to degradation. These findings suggest that impaired lipid droplet clearance, rather than accumulation, distinguishes <i>APOE4</i>-associated AD risk, and may present a new metabolic node for modulating risk."],"pubmed_title":["&lt;i&gt;APOE&lt;/i&gt; genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics."],"pubmed_authors":["Cuní-López Carla C, Root Jessica T JT, Hao Ying Y, Kowal Isabelle I, Blomberg Niek N, Ghirlando Rodolfo R, Yang Linda G LG, Koppes-den Hertog Sascha J SJ, Cookson Mark R MR, van der Kant Rik R, Giera Martin M, Qi Yue Andy YA, Narayan Priyanka S PS"],"additional_accession":[]},"is_claimable":false,"name":"APOE genotype shapes lipid droplet composition and dynamics in human astrocytes","description":"Lipid droplets are dynamic organelles involved in cellular functions ranging from lipid storage regulation to immune modulation. The proteins that localize to the lipid droplet membrane play a critical role in determining these functions. Recent research has highlighted the involvement of glial lipid droplets in the pathology and progression of late-onset Alzheimer’s disease. APOE, a gene encoding a lipid-binding and transport protein, is a major genetic determinant of Alzheimer’s disease risk, with different variants conferring risk or protection. In this study, we characterized the human astrocytic lipid droplet proteome and found that each APOE variant–risk, benign, and protective–produces a distinct proteomic profile in astrocytes. These variant-specific proteomes influence lipid droplet biology and broader aspects of cellular physiology. Moreover, we discovered that changes in the lipid droplet proteome directly affect the turnover and dynamics of lipid droplets in astrocytes across different APOE genotypes. Together, these findings provide new insights into how APOE variants reshape astrocyte biology and identify lipid droplets as a modifiable aspect of Alzheimer’s disease pathology.","dates":{"publication":"2026-07-01","submission":"2025-08-11"},"accession":"PXD067161","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:1912919","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2709072","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:109760","NEWT:29031","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:470","NEWT:5911","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:8655","NEWT:5147","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:80863","NEWT:90675","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:13489","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","NEWT:90690","NEWT:1436183","NEWT:4232","NEWT:416348","NEWT:11298","NEWT:4236","NEWT:7742","NEWT:196627","NEWT:200308","NEWT:200302","NEWT:870435","NEWT:9913","NEWT:9915","NEWT:105841","NEWT:2666255","NEWT:999810","NCBITaxon:5693","NEWT:28995","NEWT:1392998","NEWT:380394","NEWT:226900","NEWT:1266738","NEWT:231490","NEWT:244704","NEWT:7725","NEWT:9909","NEWT:9902","NEWT:430615","NEWT:563041","NEWT:72664","NEWT:36599","NEWT:41949","NEWT:326423","NEWT:452467","NEWT:198822","NEWT:36111","NEWT:326424","NEWT:1678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