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Novel diagnostic and prognostic approach for rapidly progressive dementias: Indicators based on amyloid/tau/ neurodegeneration (ATN) framework

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【Aims】:

Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs).


【Methods】:

CSF samples were collected by lumbar puncture and processed according to a standard procedure. Specifically, the CSF samples without visible blood contamination were centrifuged at 2000?× g at room temperature for 10?min, and the aliquots were then immediately frozen and stored at ?80°C until use. CSF levels of A42, Aβ40, t-Tau, and phosphorylated tau-181 (p-Tau) were measured using human Aβ and Tau ELISA kits (Innotest, United States). Fasting blood was collected between 07:00 and 09:00. The blood samples were centrifuged within an hour of collection, and serum was aliquoted into 0.5?mL polypropylene tubes and stored at ?80°C until use. All the serum samples were measured by single molecular immunity detection (SMID; Suzhou AstraBio Technology Co., Ltd, China). Informed consent was obtained before the acquisition of the CSF and blood samples. All measurements were performed by experienced laboratory technicians in a blinded approach.


Results】:

Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square?=?0.16, p =?0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square?=?0.273, p =?0.014).

DOI https://doi.org/10.1111/cns.14857