- Alzheimer Disease
Alzheimer's Disease (AD) is a degenerative disease of the central nervous system with the characteristics of insidious onset, irreversible, progressive and long course of disease. The clinical manifestations are progressive memory impairment, cognitive dysfunction, personality changes, language disorders and other neuropsychiatric symptoms. The pathological changes of the brain of AD patients are diffuse brain atrophy, and the microscopic pathological changes are mainly characterized by senile plaques (SP), neurofibrillary tangle (NFT) and neuronal loss.
AD is the seventh leading cause of death after cancer, cardiovascular disease and stroke, and can be divided into two types: early onset (FAD) and late onset (SAD). According to the International Alzheimer's Association, there are more than 50 million people with Alzheimer's disease in the world, and China has become the country with the largest number of AD patients in the world, with nearly 10 million patients. The prevalence and mortality of AD and other dementias in China are higher than the global average. With the deepening of population aging in the future, AD patients are expected to reach 78 million by 2030, which brings a heavy burden to patients' families and society.
At present, the pathogenesis of AD has not been fully elucidated and is affected by many factors, such as environment, genetics, and head trauma history. The main idea of the pathogenesis of AD is the β-amyloid (Aβ) cascade hypothesis.
Biomarkers of neurodegenerative diseases
AD Diagnosis and Biomarkers
The diagnosis of AD depends on the detection of biomarkers and neuroimaging examination combined with clinical diagnosis. Fluid and imaging biomarkers cannot be replaced by each other. There are three main clinical approaches:
(1) cerebrospinal fluid (CSF) was obtained by lumbar puncture to detect the ratio of total tau/p-tau and Aβ42 / Aβ40, which required invasive procedures.
(2) positron emission tomography (PET) imaging was performed. PET imaging is expensive and limited by equipment availability.
(3) Peripheral blood test: plasma Aβ and tau neurofilament light chain (NfL) and various inflammatory markers were detected. The blood test is less expensive, faster and easier to perform.
At present, there is no cure for Alzheimer's disease, so early prevention and intervention are particularly important.
- Tau
Tau protein is encoded by the MAPT gene, which is mainly expressed in the axons of neurons in the central nervous system. It is a microtubule associated protein (MAP) expressed in neurons. As the "scaffold" of microtubules, Tau protein participates in microtubule assembly, promotes microtubule polymerization formation and maintains microtubule stability, and is the main component of neurofibrillary tangles.
Tau exists in eight different isoform forms with more than 40 phosphorylation sites, and while phosphorylated tau has known physiological functions, hyperphosphorylation reduces its ability to bind microtubules. The hyperphosphorylated tau protein is detached from microtubules and aggregates to form neurofibrillary tangles (NTFs). This process destroys the structure of neuronal microtubules, impedes the operation of axons, impairs synaptic function, and ultimately leads to the occurrence of degenerative diseases. Neuronal fibrillary tangles (NFTS) composed of highly phosphorylated Tau protein (P-tau) are one of the hallmark pathological features of Alzheimer's disease (AD).
Different isoforms of tau (A) and post-translational modifications (B)
- P-Tau217
Tau Pathological staging
In addition to p-tau181, which has been listed as A core biomarker of AD, p-tau217 has also been confirmed to be associated with Aβ deposition.
Several studies have shown that CSF p-tau217 consistently correlates better with Aβ-PET and tau-PET than p-tau181 and can accurately detect AD. Barthelemy used quantitative mass spectrometry to achieve sensitive detection of p-tau217 and p-tau181 in CSF. A cohort of patients with AD and other neurological disorders compared with unaffected subjects showed a 6-fold increase in p-tau217 in AD patients but only a 1.3-fold increase in p-tau181, which has greater specificity and sensitivity. Similar results were obtained in the second cohort, with A sensitivity and specificity of more than 90% for CSF p-tau217 in Aβ-positive patients and a high correlation between pT217 concentrations and PiB-PET values (correlation coefficient, 0.72; P < 0.001).
CSF tau and p-tau levels in AD patients. The levels of total tau (E_Tau) and p-tau181 in CSF were detected by ELISA (a, b). CSF p-tau181 and p-tau217 levels were measured by quantitative mass spectrometry (c, d, e, and f). Red arrows indicate higher MS_p-tau 217 levels in patients with mixed dementia than in controls
In addition, a recent study showed that plasma p-tau217 can be used as a marker before the onset of clinical symptoms to distinguish asymptomatic AD from normal aging population, which is of great significance for the early diagnosis and preclinical prevention of AD patients. Jonaitis et al. used mixed-effects modeling to evaluate the agreement between plasma p-tau217 and tau-PET and the ability of p-tau217 to predict longitudinal cognitive performance in patients with preclinical AD over an 8-year follow-up. Plasma p-tau217 was significantly correlated with Aβ-PET (β^= 0.83 (0.75, 0.90), P < 0.001), and higher baseline p-tau217 levels were associated with lower cognitive trajectories (β^pTau×age = −0.07 (−0.09, −0.06), P< 0.001), and plasma p-tau217 levels are strongly associated with AD pathophysiology and prospective cognitive performance in healthy individuals.
Association of P-tau217 with longitudinal cognition. The steepest slope of panel D indicates a stronger inverse association between early p-tau217 and preclinical AD composite cognition.
- Starter Bio Recombinant antibody
pTau217 recombinant rabbit monoclonal antibody, which has higher specificity, sensitivity and stability, provides more accurate diagnostic results.
Now, Stater Bio has Tau, pTau181, and pTau217 recombinant rabbit monoclonal antibodies, welcome to contact us: info@starter-bio.com
P-Tau231 recombinant antibody is coming soon!!!
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About Us
Starter Bio (www.starter-bio.com) is a professional recombinant antibody supplier focus on CDx&IVD. We aim to provide high-quality antibody products, including IVD antigen antibodies, precision medical diagnostic antibodies, and custom services for global in vitro diagnostic enterprises and biopharmaceutical enterprises.