Team:USTC/Description
Hello, Welcome to DESCRIPTION PAGE
Introduction
Based on aptamer technology
and RPA reaction, we developed a new micro protein detection method
—captamer . It can detect protein as low as 1pg / μL, and the reaction
is very rapid, with only 20 minutes needed. We used it to detect very
small amounts of tau protein in blood, which is an important biological
index of Alzheimer's disease. It can be used for the early diagnosis of
Alzheimer's disease and make it possible to explore the dynamic changes
of blood markers of Alzheimer's disease with age, so as to lay a
foundation for the elucidation of the disease mechanism.
Project background
Alzheimer's disease (AD) is
a progressive neurodegenerative disease.
The clinical manifestations of dementia are characterized by memory
loss, aphasia, apraxia, agnosia, executive dysfunction, personality and
behavior changes.
Fig1:AD prevalence with
age and gender
Most of the patients are
50 years old and over, and the prevalence increases with age.
Fig2: Global distribution
of AD
It is estimated that
there were about 50 million patients with Alzheimer's disease
worldwide in 2018, which is similar to the population of Kenya,
Colombia or South Korea.
Fig3: Statistics and
prediction of AD patients
According to ADI
images(namely Alzheimer’s Disease International), the number of
patients with Alzheimer's disease is increasing year by year and is
expected to continue to increase in the future. The number of AD
patients will reach an amazing 150 million in 2050.
At present, the annual
cost of this disease is about $1 trillion, and it is estimated that
the cost will double by 2030. The outcome of AD is irreversible
damage to brain cells, which brings a great burden to patients and
their families. It has become a serious global medical problem.
Without effective therapy at present, once AD is diagnosed, it can’t
be cured anymore. All these mentioned above inspired us to endeavor
to find a convenient way for diagnosing AD in the early stage.
At present, the
diagnosis methods of ad mainly include scale testing, gene
detection and image assisted testing. Medical history analysis
can be carried out according to medical and family history, and
the patient can be preliminarily judged as early-onset or
late-onset venereal disease. Neurological examination can be
divided into neuropsychological evaluation, which can be carried
out through various scales and experiments, and imaging
examination includes structural magnetic resonance imaging.
Therefore, we turn our attention to biomarker detection. Perhaps
by detecting specific proteins, we can give warnings to AD
patients early.
Although the
Alzheimer disease isn’t completely understood, two major players
that are often cited in its progression are plaques and tangles.
β- Amyloid plaques can block the signal transmission between
neurons, damage the memory function of the brain, activate the
inflammatory response and further damage the surrounding
neurons. tau protein can maintain the stability of microtubules
in neuronal cells. People think that after the formation of
β-amyloid plaque, it will promote protein kinase to
phosphorylate tau protein and change its structure. Allosteric
tau proteins can no longer maintain the stability of
microtubules, but aggregate with other tau proteins. This forms
another sign of AD, neurofibrillary tangles. Neurons with
tangles and non-functioning microtubules can’t signal as well,
and sometimes end up undergoing apoptosis, or programmed cell
death. When neurons die, the brain shrinks. Some researches show
that the content of tau protein in AD patients is significantly
higher than that in normal people, so we chose tau protein as
our research object.
Fig4: Measurement of
tau protein in normal and patient blood by electrochemical
sensor
Fig5: The content of
tau protein was measured by immunological methods
Table1: Detection
method of blood markers in AD
To date, AD
biomarker-based expression techniques include mass spectrometry
(MS), magnetic resonance imaging (MRI), enzyme linked
immunosorbent assay (ELISA), Western-blot, immunohistochemistry,
flexible Multi-Analyte Profiling (xMAP) and position emission
tomography (PET).
As you can see, most
methods have various application limitations. Even ELISA, the
most practical method, can not be widely used because of its
high cost and cumbersome operation.
Therefore, it is
urgent to develop a new detection method, which can detect trace
protein, with the characteristics of low cost and fast response.
Project goals
We intend to develop
a micro protein detection method based on nucleic acid aptamer
to realize signal amplification through RPA reaction. When there
is no protein, there is no or low signal. When there is protein,
it can quickly generate monotonous fluorescent signals related
to protein concentration. Further, we plan to develop a hardware
for automatic sampling and real-time fluorescence detection, and
a software for data storage and analysis. We call this technique
captamer.