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Puja"],"technology_type":["Mass Spectrometry","Data-independent acquisition","Bottom-up proteomics"],"software":["Not available"],"submitter_keywords":["neurodegenerative diseases","retina","brain","Alzheimer's disease","3xtg-ad","Alzheimer's disease; retina; brain; neurodegenerative diseases; 3xtg-ad"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD069995"],"tissue":["Brain","Retina"],"sample_protocol":["DIA Methods – Orbitrap Exploris  Proteins were reduced, alkylated, and purified by chloroform/methanol extraction prior to digestion with sequencing grade modified porcine trypsin (Promega). Tryptic peptides were then separated by reverse phase XSelect CSH C18 2.5 um resin (Waters) on an in-line 150 x 0.075 mm column using an UltiMate 3000 RSLCnano system (Thermo). Peptides were eluted using a 60 min gradient from 98:2 to 65:35 buffer A:B ratio. Eluted peptides were ionized by electrospray (2.2 kV) followed by mass spectrometric analysis on an Orbitrap Exploris 480 mass spectrometer (Thermo). To assemble a chromatogram library, six gas-phase fractions were acquired on the Orbitrap Exploris with 4 m/z DIA spectra (4 m/z precursor isolation windows at 30,000 resolution, normalized AGC target 100%, maximum inject time 66 ms) using a staggered window pattern from narrow mass ranges using optimized window placements. Precursor spectra were acquired after each DIA duty cycle, spanning the m/z range of the gas-phase fraction (i.e. 496-602 m/z, 60,000 resolution, normalized AGC target 100%, maximum injection time 50 ms). For wide-window acquisitions, the Orbitrap Exploris was configured to acquire a precursor scan (385-1015 m/z, 60,000 resolution, normalized AGC target 100%, maximum injection time 50 ms) followed by 50x 12 m/z DIA spectra (12 m/z precursor isolation windows at 15,000 resolution, normalized AGC target 100%, maximum injection time 33 ms) using a staggered window pattern with optimized window placements. Precursor spectra were acquired after each DIA duty cycle.  Buffer A = 0.1% formic acid, 0.5% acetonitrile Buffer B = 0.1% formic acid, 99.9% acetonitrile"],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Following data acquisition, data were searched using an empirically corrected library and a quantitative analysis was performed to obtain a comprehensive proteomic profile. Proteins were identified and quantified using EncyclopeDIA (Searle et al.) and visualized with Scaffold DIA using 1% false discovery thresholds at both the protein and peptide level. Protein exclusive intensity values were assessed for quality using an in-house ProteiNorm app, a tool for systematic evaluation of normalization methods, imputation of missing values and comparisons of multiple differential abundance methods (Graw et al.). Normalization methods evaluated included log2 normalization (Log2), median normalization (Median), mean normalization (Mean), variance stabilizing normalization (VSN) (Huber et al.), quantile normalization (Quantile) (Bolstad et al.), cyclic loess normalization (Cyclic Loess) (Ritchie et al.), global robust linear regression normalization (RLR) (Chawade et al.), and global intensity normalization (Global Intensity) (Chawade et al.). The individual performance of each method was evaluated by comparing of the following metrices: total intensity, pooled intragroup coefficient of variation (PCV), pooled intragroup median absolute deviation (PMAD), pooled intragroup estimate of variance (PEV), intragroup correlation, sample correlation heatmap (Pearson), and log2-ratio distributions. The normalized data were used to perform statistical analysis using linear models for microarray data (limma) with empirical Bayes (eBayes) smoothing to the standard errors (Ritchie et al.). Proteins with an FDR adjusted p-value < 0.05 and a fold change > 2 were considered significant."],"omics_type":["Proteomics"],"labhead":["Jianhai Du"],"instrument_platform":[""],"labhead_affiliation":["West Virginia University"],"submission_type":["COMPLETE"],"species":["Mus Musculus (mouse)"],"publication":["42232055 Puja A, McNeel R, Xu R, Zhu S, Hansman D, Du J. Early proteomic signatures of Alzheimer's disease in the retina and brain of 3xTg-AD mice. Front Cell Dev Biol. 2026 14:1827348 10.3389/fcell.2026.1827348"],"submitter_mail":["ap00093@mix.wvu.edu"],"submitter_affiliation":["Graduate student"],"submitter_country":["United States"],"doi":["10.6019/PXD069995"],"pubmed_abstract":["<h4>Introduction</h4>Visual dysfunction and retinal structural changes can occur early in Alzheimer's disease (AD), but the molecular basis of these early alterations remains unclear.<h4>Methods</h4>We performed quantitative proteomic profiling of the retina and brain from 4-week-old triple-transgenic AD (3xTg-AD) mice carrying human PS1M<sub>146V</sub>, APP<sub>Swe</sub>, and tau<sub>P301L</sub> mutations, prior to detectable retinal morphological abnormalities.<h4>Results</h4>Retinal morphology was normal in 4-week-old 3xTg-AD. Proteomic analysis identified 92 significantly altered proteins in the retina and 130 in the brain, with eight proteins overlapping between tissues. These overlapping proteins included three hemoglobin subunits and five proteins involved in protein homeostasis and vesicular transport. The retinal proteome was characterized by reduced vision-related proteins, altered small-molecule transporters, and decreased levels of proteins involved in mitochondrial energetics. In the brain, prominent changes were observed in mitochondrial proteins, including respiratory chain components and mitochondrial ribosomal subunits, as well as proteins linked to autophagy and synaptic vesicle pathways.<h4>Discussion</h4>These findings identify early, common and tissue-specific proteomic changes in the retina and brain of 3xTg-AD mice prior to detectable retinal structure abnormalities. The data indicate early changes in proteins related to mitochondrial function and intracellular transport and support the use of retina as an accessible tissue for detecting preclinical AD pathology."],"pubmed_title":["Early proteomic signatures of Alzheimer's disease in the retina and brain of 3xTg-AD mice."],"pubmed_authors":["Puja Artjola A, McNeel Rachel R, Xu Rong R, Zhu Siyan S, Hansman David D, Du Jianhai J"],"additional_accession":[]},"is_claimable":false,"name":"Proteomics of the brain and retina presents early hallmarks of Alzheimer’s disease","description":"We performed proteomic profiling of the brain and retina in 3xTg-AD mouse model of Alzheimer's disease at one month of age to uncover early retinal signatures that may precede disease manifestations.","dates":{"publication":"2026-06-08","submission":"2025-10-28"},"accession":"PXD069995","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","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:6819","NEWT:475174","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:1584","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:7719","NEWT:5530","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:49928","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","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:1310173","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:2853422","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","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:1640278","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:906914","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:33941","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:42410","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:9995","NEWT:575412","NEWT:28112","NEWT:49012","NEWT:6493","NEWT:10832","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:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:1613","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:353153","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:74426","NEWT:443906","NEWT:13037","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEW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