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Validation of Retinal Abeta as a Potential Biomarker of Alzheimer's Disease

验证视网膜 Abeta 作为阿尔茨海默病的潜在生物标志物

基本信息

批准号：
10670340
负责人：
Wellington Pham
金额：
$ 69.85万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10670340
关键词：
Address Aerosols Affinity Alzheimer disease detection Alzheimer&apos s Disease Alzheimer’s disease biomarker Amyloid beta-Protein Binding Biodistribution Biological Assay Blood Brain Cerebral cortex Cessation of life Chemicals Collaborations Community Health Curcumin Data Dementia Deposition Detection Disease Disease Progression Dose Drug Delivery Systems Early Diagnosis Early Intervention Elderly Excretory function Eye Fluorescence Formulation Foundations Goals Hippocampus Image Inhalation Kinetics Lead Logic Memory Loss Metabolism Methods Modification Molecular Profiling Molecular Target Monitor Mus Nerve Degeneration Neurons Onset of illness Ophthalmology Pathology Patients Peptides Persons Pharmaceutical Chemistry Pharmaceutical Preparations Proteins Reporting Reproducibility Retina Safety Senile Plaques Signal Transduction Specificity Surrogate Markers Technology Testing Tissues Toxic effect Validation Work abeta accumulation absorption aerosolized analog chemical genetics cohort community setting cost early detection biomarkers early onset extracellular functional group high reward high risk improved in vivo in vivo evaluation in vivo imaging microscopic imaging molecular imaging neuron loss novel novel strategies potential biomarker professor response retinal imaging routine screening screening therapy outcome tool

项目摘要

PROJECT SUMMARY This application addresses the overarching challenge of detection of the early onset of β-amyloid plaques (Abeta) in Alzheimer's disease (AD). It does so by proposing a novel approach to image retinal Abeta by using signals emitted by curcumin fluorescence (FL). AD is the most common cause of dementia among elderly people. Its pathology is characterized by the presence of extracellular deposits of misfolded and aggregated Abeta peptides, which subsequently spread from the hippocampus to the cerebral cortex causing neuronal death and ultimately loss of memory, logic and the ability to speak. At present, no disease-modifying therapy is effective against AD nor it is possible to diagnose the early onset and/or the progress of the disease. Recent findings indicate that elevated levels of Abeta proteins are associated with dysfunctional neuronal networks both in the brain and eyes. Because AD undergoes a protracted asymptomatic stage before it reaches the advanced stage, a window of opportunity exists for early intervention, and successful detection of the early onset of the disease via routine screening will improve therapeutic outcomes and save lives. In that regard, early detection of Abeta in the eyes at ophthalmology centers, widely available in every health community settings seems ideal in terms of practicality, feasibility, safety and cost. Recently, our group demonstrated a novel approach for delivery of curcumin in vivo via inhalation of the curcumin aerosol. Further, in collaboration with Professor Joanne Matsubara, we recently demonstrated that inhaling curcumin aerosol resulted in significant accumulation of the compound in the retina. Further, we also demonstrated that curcumin binds to Abeta in retinal sublayers. Building on that foundation, we hypothesize that curcumin FL in the eyes can be used as a surrogate biomarker for assessing Abeta levels in the brain. Our long-term objective is to (i) demonstrate the newly synthesized curcumin analogs can be distributed and bind effectively to retinal Abeta; (ii) demonstrate retinal Abeta as a early biomarker of AD. A less well developed, but potentially powerful approach, marrying medicinal chemistry with drug delivery, and targeted molecular imaging, for high sensitivity molecular “fingerprinting” of AD in vivo, is the subject of this high risk-high reward proposal.

项目总结

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer's disease.

DOI：
10.1002/1873-3468.14303
发表时间：
2022-05
期刊：
FEBS letters
影响因子：
3.5
作者：
通讯作者：

Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.

DOI：
10.1186/s40478-022-01448-y
发表时间：
2022-10-05
期刊：
Acta neuropathologica communications
影响因子：
7.1
作者：
通讯作者：

Inhalable Thioflavin S for the Detection of Amyloid Beta Deposits in the Retina.

DOI：
10.3390/molecules26040835
发表时间：
2021-02-05
期刊：
Molecules (Basel, Switzerland)
影响因子：
0
作者：
Barton SM;To E;Rogers BP;Whitmore C;Uppal M;Matsubara JA;Pham W
通讯作者：
Pham W

SPECHT: Self-tuning Plausibility based object detection Enables quantification of Conflict in Heterogeneous multi-scale microscopy.

DOI：
10.1371/journal.pone.0276726
发表时间：
2022
期刊：
PLOS ONE
影响因子：
3.7
作者：
Cardoen, Ben;Wong, Timothy;Alan, Parsa;Lee, Sieun;Matsubara, Joanne Aiko;Nabi, Ivan Robert;Hamarneh, Ghassan
通讯作者：
Hamarneh, Ghassan

MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer's disease.

DOI：
10.26508/lsa.202201757
发表时间：
2023-06
期刊：
LIFE SCIENCE ALLIANCE
影响因子：
4.4
作者：
Wijesinghe, Printha;Xi, Jeanne;Cui, Jing;Campbell, Matthew;Pham, Wellington;Matsubara, Joanne A.
通讯作者：
Matsubara, Joanne A.