Dataset Information

Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid

ABSTRACT: Accurate diagnosis of Alzheimer’s disease (AD) in its earliest stage can prevent the disease and delay the onset of symptoms by maintaining a healthy lifestyle and controlling modifiable risk factors. Therefore, more sensitive, relatively inexpensive, non-invasive, and simple screening tools are required for the early diagnosis and progression monitoring of AD. Here, we designed a self assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Multiple simultaneous captures and magnetic separation of biomarkers and target-specific fluorophore emission induced a one-tomulti signal, resulting in a low detection limit (236 aM), good reliability (R2 = 0.991), and wide analytical range (0.320–1000 fM) for APOE and CAP1 biomarkers in human serum and tear fluid. More importantly, SNAFIA successfully differentiated AD patients from healthy controls with 90% sensitivity and 100% specificity in less than 1 h in 39 clinical tear samples. As an easily accessible diagnostic tool with fast and accurate results, SNAFIA can help diagnose AD early to aid in long-term care planning, increase the efficiency of clinical trials, and dramatically accelerate therapeutic development.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tear

DISEASE(S): Alzheimer's Disease

SUBMITTER: Chae Eun Moon

LAB HEAD: Yong Woo Ji

PROVIDER: PXD042142 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer's disease from tear fluid.

Lee Sojeong S Kim Eunjung E Moon Chae-Eun CE Park Chaewon C Lim Jong-Woo JW Baek Minseok M Shin Moo-Kwang MK Ki Jisun J Cho Hanna H Ji Yong Woo YW Haam Seungjoo S

Nature communications 20231209 1

Accurate diagnosis of Alzheimer's disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase ...[more]

PMID: 38071202

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Project description:Glycosylation of proteins is one of the most common post-translational modification (PTM) and plays important regulatory functions in diverse biological processes such as protein stability or cell signaling. Accordingly, glycoproteins are also a consistent part of the human tear film proteome maintaining the proper function of the ocular surface and forming the first defense barrier of the ocular immune system. Irregularities in the glycoproteomic composition of the tear film might promote development of chronic eye diseases indicating glycoproteins as valuable source for biomarker discovery or drug target identification. The present study aimed to develop a lectin-based affinity method for the enrichment and concentration of tear glycoproteins/glycopeptides and the characterization of their specific N-glycosylation sites by high-resolution mass spectrometry (MS). For method development and evaluation, we accumulated first native glycoproteins from human tear sample pools and assessed the enrichment efficiency of different lectin column systems by 1D gel electrophoresis and specific protein stainings (Coomassie and glycoproteins). The best-performing multi-lectin column system (comprising the four lectins ConA, JAC, WGA and UEA I, termed as 4L) was applied for glycopeptide enrichment from human tear sample digests followed by MS-based detection and localization of their specific N-glycosylation sites. As main result, the present study identified in total 26 N glycosylation sites of 11 N-glycoproteins in tear sample pools of healthy individuals (n=3 biological sample pools). Amongst others, we identified tear film proteins lactotransferrin (N497 and N642, LTF), Ig heavy chain constant α-1 (N144 and 340, IGHA1), prolactin-inducible protein (N105, PIP) as well as extracellular lacritin (N105, LACRT) as highly reliable and significant N glycoproteins, which were already associated with the pathogenesis of various chronic eye diseases such as the dry eye syndrome (DES). In conclusion, the results of the present study will serve as important tear film N-glycoprotein catalogue for future studies focusing the human tear film and ocular surface-related inflammatory diseases.

Dataset Information

Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid

Publications

Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer's disease from tear fluid.

Similar Datasets

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