Near Infrared Fluorescence Probes For Diagnosis Of Alzheimer’s Disease
Project Description :

Alzheimer’s disease (ad) is a major contributor of dementia with no early diagnosis techniques and clinically accepted treatment to cure or halt the progression. accumulation of fibrillar aggregates (aβ plaques) of aβ peptides in the brain is one of the main causes of alzheimer’s disease (ad). the neurodegeneration and subsequent progressive deterioration in cognitive ability are hallmark symptoms of this incurable syndrome. the aβ aggregates occur much earlier in brain before any cognitive symptoms are observed, making it a promising biomarker for ad diagnosis. one of the major problems in the diagnosis of ad is the lack of effective methods for the selective detection of aβ aggregates. nir probes exhibit greater penetration depth (in in vivo studies), emission in longer wavelength and minimum background fluorescence, which make them ideal candidates for various in vitro and in vivo studies in molecular biology and biotechnology applications. here we have designed and synthesized near infrared (nir) turn on fluorescence probes (tc and qc) for selective and specific detection of aβ aggregates, and aβ plaques in human brain tissue. nir probes (tc and qc) specifically bind to aβ aggregates and exhibit ~30 fold turn on fluorescence enhancement (fig1). both tc and qc exhibits nanomolar binding affinity’s towards the aβ aggregates [58 nm (tc) and 82 nm (qc)] and have one order higher binding affinity compared to commercially available dyes such as tht and congo red. both the probes tc and qc have shown high selectivity towards the aβ aggregates over other toxic aggregates involved in different diseases (parkinson’s disease, huntingtin, amyotrophic lateral sclerosis and frontotemporal dementia). various types of fluorescence probes are reported in literature for detecting aβ aggregates or aβ plaques in brain, but they lack selectivity and provide minimum information on the specific disease condition, were as our probes being selective and specific to aβ aggregates would be a good lead for developing commercial diagnostic probe for ad. in ad along with aβ peptide, tau protein is phosphorylated which misfold and aggregates to form neurofibrillary tangles (nfts). tau and nfts are independently involved in many other neuronal disorders such as, supranuclear palsy, frontotemporal dementia among others. therefore, selective detection of aβ plaques over nfts is crucial for accurate diagnosis of ad. remarkably, cq selectively stains aβ plaques in human brain tissue over nfts of tau protein, a highly desirable attribute to distinguish disease condition caused by tau aggregation from ad. further we stained ad brain tissue were both the cq and ths (control dye used to stain ad brain tissue) were used to stain a plaques in human brain tissue. the concentration of cq required for staining a plaques was 1000-fold less than that of ths. moreover, cq stain responded to de-staining better than ths, which resulted in a significant decrease in background fluorescence, indicating higher sensitivity for β aggregates than ths (fig2). ad brain tissue stained with cq and phf1 antibody (selective to nfts), were analysed through microscopy. the merged image confirmed that cq selectively binds to a plaques and has no overlap staining with phf1 antibody (fig3). we were also successful in detecting aβ aggregates in a series of cerebral spinal fluid (csf) samples using our nir probe. further, we are trying to determine the concentrations of aβ aggregates in csf samples to develop standard charts, which could be used as reference for analysing unknown csf samples and can further be developed for diagnosis ad in early stage. aforementioned attributes make our nir probes ideal candidates for developing them as diagnostic tools for early diagnosis of ad and understand its progression for developing new therapeutic strategies.

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Project Details :
  • Date : Nov 23,2016
  • Innovator : K Rajasekhar
  • Team Members : Prof. T. Govindaraju,Prof. Kavita Shah
  • Guide Name : Prof. T. Govindaraju
  • University : Jawaharlal Nehru Centre for Advanced Scientific Research
  • Submission Year : 2017
  • Category : Biological Sciences & Bioengineering
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