"Alzheimer's disease" marker – a hot project on the rise

Research background

Alzheimer's disease (AD) is an insidious and slow-degenerative disease that is the most common form of senile dementia, accounting for an estimated 60 to 80 percent of total dementia cases [1].

Short-term memory impairment is the most common early symptom of AD, and its hallmark pathological features are neurofibrillary tangles caused by amyloid plaque deposition outside brain neurons and hyperphosphorylation of tau protein inside neurons
.
With the development of the disease, patients gradually lose their ability to communicate, judge, sense of direction and self-care of life, and eventually lose language function, mobility and swallowing ability [1].

As of 2015, 46 million people worldwide had AD
.
The number of people affected worldwide is expected to increase to 130 million by 2050, with total healthcare costs exceeding US$1 trillion, meaning that AD healthcare alone could make the world's 18th largest economy[2].

At present, there are more than 10 million AD patients in China and will maintain rapid growth
.
It is estimated that by 2030, the number of AD patients in China will reach about 16 million
.
China has become the country
most affected by AD.
Therefore, in-depth study of the etiology and pathological mechanism of AD and accelerating the development of effective AD prevention and treatment programs have become an important task
for neurologists and biomedical enterprises in China and even around the world.

Figure 1.
Global impact of Alzheimer's disease[2]

The onset of AD is insidious and usually develops 15 to 20 years or more before diagnosis is confirmed, a stage known as the "preclinical phase" of AD [3].

As the course of the disease progresses, patients develop a "mild cognitive impairment" (MCI), in which symptoms develop and worsen, progressing to "mild dementia", "moderate dementia", and "severe dementia" [4-7].

Due to the lack of specificity of early symptoms, it is difficult to achieve early detection and early treatment
of AD patients.
AD can eventually be fatal, with most patients having a life expectancy of only 4-8 years
after diagnosis.

Figure 2.
Duration of Alzheimer's disease[1]

In recent years, the research on AD has been increasingly deepened, especially the progress of cerebrospinal fluid (CSF) markers and imaging methods, which effectively improves the accuracy of
AD diagnosis 。 The General Office of the National Health Commission issued the "Guidelines for the Diagnosis and Treatment of Alzheimer's Disease (2020 Edition)": it is recommended to conduct a series of clinical evaluations for suspected patients, including biomarker examinations: decreased levels of β amyloid 42 (1-42) (Aβ42) in cerebrospinal fluid, and increased
levels of total Tau protein and phosphorylated Tau protein (phospho-Tau, p-Tau).

Standards for the diagnosis and treatment of Alzheimer's disease (2020 edition)

Marker analysis

Alterations in AD biomarker levels often occur in the preclinical phase
.
In addition to imaging, CSF biochemical analysis is a common tool for AD screening[1].

CSF in a significant number of AD patients reveals a decrease in soluble β-amyloid (A β β), particularly Aβ42, while total Tau and p-Tau levels rise
.
CSF Neurofilament Light-chain (NF-L) is an emerging biomarker
.
NF-L is distributed inside
nerve cells under physiological conditions.
Thus, an abnormal increase in NF-L released into CSF is thought to indicate the cause
of neurocyte degeneration [8,9].

Due to the presence of the blood-brain barrier, biomarkers in the brain are difficult to efficiently enter the peripheral blood circulation, so CSF samples can provide more valuable information for clinical diagnosis of AD than serum samples [10].

The decrease in Aβ42 content in CSF is the earliest change, usually detected years before patients develop significant cognitive impairment, and has high diagnostic sensitivity, making it valuable for early screening for AD [11].

For the diagnostic kit products of AD markers, many companies have obtained medical registration certificates and have become hot projects
for development.

Introduction of raw materials for Boorsen AD markers

Given that Alzheimer's disease (AD) markers are generally difficult to identify most sites and clinical samples and standards are not readily available, the development of AD marker IVD raw materials is more difficult
than that of conventional IVD raw materials.
Over the past 20 years, Beijing Bioss Bioss Co.
, Ltd.
(Bioss) has never given up the research and development of AD marker raw materials, optimized step by step, and continuously upgraded, and has now launched mature IVD paired antibody products
.

Boosen Aβ series IVD antibodies

Compared with the decrease in Aβ42, the significant increase in total Tau and p-Tau in CSF occurred later in the disease process, very close to the time of onset of clinically detectable dementia symptoms [11].

Therefore, Tau protein-related biomarkers are difficult to play a key role
in early AD screening.
The significance of detecting Tau in CSF is to make up for the poor specificity of
Aβ in a single test.
There are many Tau phosphorylation sites that promise to become AD biomarkers for CSF, and the more studied is threonine 181 phosphorylated tau (p-Tau181).

After years of optimization, the combined interpretation of Aβ42, total Tau and p-Tau181 in CSF reached a threshold of 80% in sensitivity and specificity[12].

Boorsen Tau series IVD antibodies

NF-L is another important marker of neuronal integrity, reflecting axon damage in the white matter
.
Therefore, NF-L is considered an important marker for a variety of neurodegenerative diseases, including AD [13-15].

Since NF-L level is highly correlated with nerve cell damage, the combination of NF-L content in CSF and classical indexes can further improve the specificity and sensitivity of diagnosis, and provide more basis for the division of AD pathological development stage [16].

In addition, NF-L is currently the only marker that has been shown to transfer directly from cerebrospinal fluid to plasma [17].

Therefore, measuring the patient's serum NF-L level before taking CSF may be a better way
to reduce patient distress and improve the efficiency of medical resource use.

Boosen NF-L series IVD antibodies