JAMA Neurology: In the blood, the phosphorylated tau protein is different, and the clinical prediction significance is different

 

Neurofibrillary tangles composed of hyperphosphorylated tau in neurons are one of the hallmark pathological features of Alzheimer's disease (AD)
.

An immunoassay to measure threonine 181 phosphorylated tau (p-tau181) in cerebrospinal fluid (CSF) has been developed as a biomarker of neurofibrillary tangles to support the clinical diagnosis of AD dementia and as a predictor A predictor of progression from no cognitive impairment (CU) to mild cognitive impairment (MCI)

Immune diagnosis

However, there are many tau phosphorylation sites that show promise as CSF AD biomarkers, including p-tau181, p-tau217, and p-tau231
.

Compared with the brain or blood, some of the p-tau species may be enriched in CSF to a different degree, but the species with the strongest plasma-CSF correlation has been shown to be driven by amyloid and have a greater impact on AD pathology.

In the past two years, some studies have shown that plasma p-tau181, p-tau217 and p-tau231 are indicators of amyloid and tau pathology in the clinical AD spectrum, which can distinguish AD dementia from other neurodegenerative diseases Come
.

Plasma p-tau181, p-tau217 and p-tau231 are indicators of amyloid and tau pathology in the clinical AD spectrum, which can distinguish AD dementia from other neurodegenerative diseases
.

Plasma p-tau217 has better accuracy in distinguishing AD dementia than p-tau181
.

Although p-tau181, p-tau217, and p-tau231 are closely related in CSF, these p-tau types or platforms for measuring them are required, especially Meso Scale Discovery (MSD; Meso Scale Diagnostics) and single Molecular arrays (Simoa; Quanterix Corporation) are compared in blood samples

In this way, Michelle M.
Mielke of Mayo Clinic et al.
evaluated the plasma p-tau181 and p-tau231 (measured on the Simoa platform) and p-tau181 and p-tau181 and p-tau231 of patients without dementia who participated in the Mayo Clinic Aging Study (MCSA).
p-tau217 (measured on the MSD platform) was compared
.

Amyloid results include positron emission tomography (PET), tau positron emission tomography, magnetic resonance imaging (MRI) and cerebral neurodegenerative vascular measurements pathology, as well as cognitive ability and overall specific areas

Blood vessel

They used a logistic regression model to analyze the relationship between four plasma p-tau indicators and amyloid PET, metaregion of interest tau PET (metaregion of interest tau PET), and entorhinal cortex tau PET
.

Finally, the ROC curve is used to evaluate the accuracy of the prediction

Main clinical outcomes: amyloid (normalized uptake ratio greater than 1.

48) and tau PET, white matter hyperintensity, white matter microstructural integrity (score anisotropy of the corpus callosum and hippocampal dentate tract), and cognitive ability

Among the 200 participants included, 101 (50.

5%) were male, and the median (interquartile range [IQR]) age was 79.

Compared with amyloid-negative CU participants, among amyloid-positive CU participants, the median (IQR) Simoa p-tau181 measurement was 49% higher (2.
58 [2.
00-3.
72] vs 1.
73 [1.
45] -2.
13] pg/ml), the MSD p-tau181 measurement value was 53% higher (
1.
22 [0.
91-1.
56] vs 0.
80 [0.
66-0.
97] pg/mL), the MSD p-tau217 was 77% higher (0.
23 [ 0.
17-0.
34] vs 0.
13 [0.
09-0.
18] pg/mL), while Simoa p-tau231 is 49% higher (20.
21 [15.
60-25.
41] vs 14.
27 [11.
27-18.
10] pg/mL)
.

There is no difference between the p-tau species of amyloid PET and tauPET meta-regions
.

There is no difference between the p-tau species of amyloid PET and tauPET meta-regions
.

However, among CU participants, both MSD p-tau181 and MSD p-tau217 predicted abnormal entorhinal cortex tau PET more accurately than Simoa p-tau181 (MSD p-tau181: AUROC, 0.
80 vs 0.
70; P = .
046 ; MSD p-tau217: AUROC, 0.
81 vs 0.
70; P = .
04
.

MSD p-tau181 and p-tau217 and Simoa p-tau181, but not p-tau231, are related to greater white matter high density volume and lower white matter microstructural integrity
.

It is related to larger white matter high density volume and lower white matter microstructure integrity
.

The important significance of this study lies in the discovery: in asymptomatic people, different plasma p-tau types and platforms have subtleties in predicting amyloid and tau PET, as well as MRI measures related to cerebrovascular and Alzheimer's disease.
Difference
.

In asymptomatic people, different plasma p-tau types and platforms have subtle differences in predicting amyloid and tau PET, as well as MRI measures related to cerebrovascular and Alzheimer's disease
.

 

Original Source:
Mielke MM, Frank RD, Dage JL, et al.
Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes.
JAMA Neurol.
Published online July 26, 2021.
doi: 10.
1001/jamaneurol.
2021.
2293

Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes.
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