ABSTRACT
Purpose: This study aimed to evaluate the use of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the diagnosis of Alzheimer's disease (AD) and the differential diagnosis between AD and mild cognitive impairment (MCI). Methods: From September 2021 to October 2022, we collected venous blood from patients and healthy individuals who visited our hospital's Neurology Department, and we isolated serum to detect NfL and GFAP using direct chemiluminescence. The results were analyzed using one-way analysis of variance (ANOVA) analysis and receiver operating characteristic (ROC) curves. Results: Pairwise comparisons among the three groups showed that compared with the health checkup (HC) group, serum NfL and GFAP were increased in both AD and MCI (PNfL < 0.05, PGFAP < 0.01). There were significant differences in GFAP between MCI and AD groups, and the level in AD group was higher (p < 0.01), while there was no difference in NfL. Both serum NfL and serum GFAP levels can independently diagnose AD (p < 0.01). The ROC curve showed that GFAP had a higher diagnostic efficacy, with an area under the ROC curve (AUC) of 0.928. The cut-off values of the two serum markers for the diagnosis of AD were NfL > 40.09 pg./mL and GFAP >31.40 pg./mL. Sensitivity and specificity for NfL in the diagnosis of AD were 59.6 and 76.2%, respectively, and for GFAP, they were 90.4 and 82.1%, respectively. The combined diagnosis of GFAP and NfL improved the diagnostic efficiency (AUC = 0.931, sensitivity = 78.8%, specificity = 92.3%). The cut-off value of GFAP for the differential diagnosis of MCI and AD was 46.05 pg./mL. Conclusion: Both serum NfL and serum GFAP can be used as biomarkers for the diagnosis of AD. Serum GFAP has better diagnostic efficacy and can distinguish AD from MCI. A combined diagnosis can improve diagnostic specificity.
ABSTRACT
In order to realize the early diagnosis of Alzheimer's disease (AD), we designed and synthesized a series of multi-fluorine labeled indanone derivatives based on indanone which could target ß-amyloid (Aß). Through the in vitro staining experiment and affinity experiment, we selected 7d out, and then evaluated it through other in vivo and in vitro experiments. The staining of AD human brain adjacent sections revealed that compound 7d could bind to Aß plaques with high affinity. In the in vitro binding assay, 7d showed a balanced affinity with Aß1-40 (Kd = 367 ± 13) and Aß1-42 (Kd = 384 ± 56). Also, 7d exhibited a low toxicity (LD50 > 50 mg/kg) and an excellent ability to pass through the blood-brain barrier (Log p = 3.87). The biodistribution experiment in mice showed that 7d reached the highest brain uptake after 1 h of tail vein injection and cleared after 24 h. A low concentration of 7d (1.875 mg/ml) showed a strong imaging ability (19F-weighted mode), and the imaging capability increased with the increasing of concentration. All the results showed that 7d could provide a feasible solution for the early diagnosis of AD under non-radioactive condition.
