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Alzheimer's disease (AD) has two pathological features: amyloid β (Aβ) plaques and tau neurofibrillary tangles
.
In living individuals, these pathologies can be detected by positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) analysis, using immunoassays to measure Aβ42 (or Aβ42/Aβ40 ratio), total tau, and phosphorylated tau-181 (p -tau 181)
Alzheimer's disease (AD) has two pathological features: amyloid β (Aβ) plaques and tau neurofibrillary tangles
CSF p-tau181 is highly specific to AD pathology and has no changes in pure tau diseases including tau-related frontotemporal degeneration
Aβ pathology is the earliest detectable change in AD, and the established p-tau181 becomes abnormal in the late stage of mild cognitive impairment (MCI) and dementia
.
However, animal model studies have shown that with the appearance of Aβ pathology, other forms of p-tau may increase in the early stages of the disease process
Aβ pathology is the earliest detectable change in AD, and the established p-tau181 becomes abnormal in the late stage of mild cognitive impairment (MCI) and dementia
The correlation between P-tau 217 and Aβ pathology is better than that of p-tau181, and it is helpful to distinguish AD and non-AD diseases
Researchers evaluated Np-tau217, Np-tau181, and standard mid-region p-tau181 (Mid-p-tau181) biomarkers in three cohorts (n = 503) to assess diagnostic performance, consistency and compatibility Association of Amyloid Beta Protein (Aβ)
.
The results showed that the consistency (88.
2%) between Np-tau217 and Np-tau181 in cerebrospinal fluid was better than mid-p-tau 181 (79.
7%-82.
7%)
.
Np-tau217 and Np-tau181 increased in early mild cognitive impairment (MCI)-AD (A+T-N –), while Mid-p-tau181 remained unchanged until AD-dementia
The consistency (88.
In both validation cohorts, β42 decreased in MCI-AD patients
.
Individuals with AD-dementia have AD cerebrospinal fluid characteristics based on a defined cut-off value
Np-tau217 and Np-tau181 determined the pathophysiology of Aβ (area under the curve [AUC] = 94.
8%-97.
1%), and were significantly better than Mid-p-tau181 (AUC = 91.
2% and 70.
6%), distinguishing MCI- AD and non-AD MCI (AUC = 82.
6%–90.
5%)
.
P-tau biomarkers equally distinguish between AD and non-AD dementia (AUC = 99.
P-tau biomarkers equally distinguish between AD and non-AD dementia (AUC = 99.
The aliquots from two different cerebrospinal fluid samples were analyzed for untreated (pure) or immunodepleted analysis using the capture and detection antibody (IP'ed) used in the Np-tau217 test
.
.
In summary, Np-tau217 and Np-tau181 can improve the diagnostic accuracy of prodromal AD and clinical trial recruitment, because both are better than Mid-p-tau181 in identifying Aβ pathophysiology and identifying early MCI-AD
.
.
In summary, Np-tau217 and Np-tau181 can improve the diagnostic accuracy of prodromal AD and clinical trial recruitment, because both are better than Mid-p-tau181 in identifying Aβ pathophysiology and identifying early MCI-AD
.
references:
Head-to-head comparison of clinical performance of CSFphospho-tau T181 and T217 biomarkers for Alzheimer'sdisease diagnosis.
https://doi.
org/10.
1002/alz.
12236
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