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!