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Pechakucha talk on Alzheimer's diagnosis
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Transcript of Pechakucha talk on Alzheimer's diagnosis
New diagnosis method for Alzheimer’s
using curcumin-conjugated magnetic nanoparticles with in vivo MRI
By Ka Yan Chan (Kathy)
Alzheimer’s disease
• The most prevalent neurological condition• Characterized by progressive impairment in cognitive
function and behaviour• Listed as the sixth leading cause of death in the US• Yet no cure or prevention has been found
Pathological hallmark
• Plaques – formed by extracellular accumulation of amyloid β (Aβ) peptides between nerve cells
• Tangles – twisted fibers formed by tau proteins that build up inside cells
99.6% failure in clinical trials!
• Between 2002 and 2012, only 1/244 tested drugs were approved success rate 0.4%
• Why? change of Aβ level begins in the cerebrospinal fluid (CSF) ∵at least 20 years before the expected onset of medical symptoms
Recent Approach
• Early intervention that stop the neurodegeneration before the damage becomes irreversible
• This requires a sensitive and accurate diagnostic technique to detect the Aβ plaques before the appearance of any cognitive symptoms
Current screening methods
• CSF analysis – require an invasive lumbar puncture that most asymptomatic individuals would not risk to undergo
• PET scan – radioactive and too expensive for most people to afford
• MRI – free of radiation, high resolution, widely available in clinical setting
concerns
MRIContrast agent/ Amyloid specific
probes
Aβ specific tracer: Aβ1-42 peptide
neurotoxic, could initiate further Aβ deposition, making it unideal for
clinical trials
?
curcumin-conjugated magnetic nanoparticles (Cur-MNPs)
• natural compound extracted from turmeric• Not only it can bind to both Aβ plaques, but also it is a
potential treatment of AD by disaggregating Aβ• better alternative as an amyloid specific probe
Current study
• However, the study did not perform in vivo MRI testing
Injection of Cur-MNPs
AD transgenic mice +
control miceEx vivo MRI Immunohistolog
y
Amyloid plaques
detected!
Proposal
Cur-MNPs
In vivo MRI
Early diagnosis
of AD
Theory / Rationale
Cur-MNPs
Ex vivo MRI
Amyloid plaques
visualized
Aβ1-42 peptide
In vivo MRI
Amyloid plaques
visualized
Cur-MNPs
In vivo MRI
Amyloid plaques
visualized
Hypothesis
Cur-MNPs In vivo MRI
Amyloid plaques
visualized!
Experimental Design
• Step 1: making nanoparticles
Reverse co-precipitation
method
Synthesize superparamagnetic
nanoparticles
Conjugate with curcumin
Experimental Design
• AD transgenic mice: carry the Aβ precursor protein (APP)
• wild type control mice: non-transgenic, same age
AD transgenic mice and wild type
control mice
Cur-MNPs
• Step 2: injection of Cur-MNPs
Experimental Design
• Step 3: in vivo MRI
In vivo MRIAnesthetize the mice
Experimental Design
• Step 4: in vivo MRI imaging• After injection: in vivo images taken every 2 hrs (3 times)• record the progression of Aβ plaques staining • optimize the injection time for future clinical trials
Experimental Design
• Step 5: ex vivo MRI image• For comparison with the in vivo MRI images of
Aβ plaques visibility
Ex vivo imagesImmunohistology
Implication
• Clinical trials ✔• Drug development ✔• Cure Alzheimer’s disease ✔
Implication
• The success of this research could make Cur-MNPs a non-invasive diagnostic method for pre-symptom AD patients
• It would be a HUGE breakthrough in the development of potential AD drugs and cure!