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Additional file 1: Supplementary Table 1. Baseline characteristics of the total participants according to the initial serum NFL levels. Supplementary Table 2. Multivariate Cox regression analysis of the factors for cognitive stage transition in total participants. Supplementary Table 3. Clinical characteristics of participants based on cognitive stage transition over the study period in mild cognitive impairment participants (n = 53). Supplementary Table 4. Clinical characteristics of participants based on cognitive stage transition over the study period in cognitively unimpaired participants (n = 146). Supplementary Table 5. Correlation between cortical thickness and neurofilament light chain levels in the serum. The cortical thickness of specific brain regions, including the hippocampus, globus pallidus, accumbens, putamen, and thalamus, were significantly negatively correlated with serum NFL levels. Supplementary Table 6. Clinical characteristics of participants with negative amyloid pathology according to the initial serum NFL levels (n = 135). Higher serum NFL levels in individuals with negative amyloid pathology were associated with cognitive stage transition (P = 0.003).

Additional file 1. Clinical trial protocol.

Additional file 2: Table S1. Inclusion and exclusion criteria of this clinical trial. Table S2. Participant number of each group. Table S3. Observed mean total score of each outcome. Table S4. Summary of CIBIS and CIBIC-plus distributions in full analysis set. Table S5. Least mean difference from placebo in full analysis set. Table S6. Least mean difference from placebo in per-protocol population. Table S7. Overall summary of treatment-emergent adverse events: safety set population. Table S8. Most frequent treatment-emergent adverse events that occurred in > 2 patient overall: safety set population. Figure S1. GV1001 (1 mg/kg) or an equivalent volume of 0.9% saline was subcutaneously injected into old 3xTg-AD mice (B6:129-Psen1tm1Mpm Tg[APPSwe, tauP301L]1Lfa/Mmjax) from the age of 21 months until the mice were deemed ready for sacrifice according to the CCAC guidelines on selecting an appropriate endpoint in experiments using animals for research, teaching, and testing. The injections were administered three times a week until the endpoint. The neurobehavioral functions were evaluated every 3 days until the endpoint using the Y-maze test and passive avoidance task. A. In the Y-maze test, which was used to measure the willingness of rodents to explore new environments and therefore quantify the cognitive deficits,1,2 compared with 0.9% saline, 1 mg/kg GV1001 significantly improved the percentage of spontaneous alternations among the Y-maze arms. B and C. In the passive avoidance tasks, which is a fear-aggravated test used to evaluate learning and memory, the mice received an electric shock when they entered the dark compartment3,4; therefore, the latency to enter the dark compartment and number of errors reflected the learning and memory of the mice. The latency to enter the dark compartment and number of errors were significantly improved following treatment with 1 mg/kg GV1001 (B and C, respectively). D. To confirm that GV1001 can enter the brain, 1 mg/kg of GV1001 conjugated with ferrocenecarboxylic acid, which we used in our previous study,5 was subcutaneously injected into 3xTg-AD (12-month-old) mice. It was detected as dark signals in the brain using 3 T magnetic resonance imaging (white arrows) and Prussian blue staining (black boxes).

Background Although gait disturbances are relatively common symptoms in diabetic polyneuropathy (DPN), few studies have quantitatively analyzed gait and posture in DPN patients. This study aimed to analyze gait and posture quantitatively in DPN patients and to determine the association between clinical and electrophysiological parameters and gait and posture parameters. Methods Sixty-four DPN patients were enrolled in this study. DPN was clinically assessed using the Toronto clinical neuropathy score (TCNS). All participants underwent nerve conduction study (NCS), three-dimensional motion analysis, and static posturography. We evaluate the correlation of gait and posture parameters with electrophysiological and clinical parameters. Results Foot height, step length, and stride length among gait parameters were inversely correlated with the TCNS. Anteroposterior range during eyes-closed and mediolateral distance and range during eyes-open and eyes-closed were inversely correlated with the sensory nerve action potential amplitude in the sural nerve. Mediolateral distance during eyes-open and eyes-closed was correlated with the compound muscle action potential amplitude in the peroneal nerve. Conclusions Gait parameters are associated with clinical parameters, and postural parameters are associated with electrophysiological parameters, particularly sensory NCS. Gait and postural analysis can be a useful tool for assessing the neurological status in DPN patients.