Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer’s disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ_1–42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression.

Background: Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. Methods: This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received—placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 12 weeks. Results: Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P =0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92–2.60) between the placebo and low-dose groups and 1.61 (0.94–2.76) between the placebo and high-dose groups. No serious adverse events were reported. Conclusions: The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0–2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT02831088.

Forward head posture (FHP) is a common postural problem experienced by most people. However, its effect on brain activity is still unknown. Accordingly, we aimed to observe changes in brain waves at rest to determine the effect of FHP on the nervous systems. A total of 33 computer users (Male = 17; Female = 16; age = 22.18 ± 1.88) were examined in both FHP and neutral posture. For each session, brain waves were measured for 5 min, and then muscle mechanical properties and cranio-vertebral angle (CVA) were measured. Changes in brain waves between the neutral posture and FHP were prominent in gamma waves. A notable increase was confirmed in the frontal and parietal lobes. That is, eight channels in the frontal lobe and all channels in the parietal lobe showed a significant increase in FHP compared to neutral posture. Additionally, FHP changes were associated with a decrease in CVA (p < 0.001), an increase in levator scapulae tone (Right, p = 0.014; Left, p = 0.001), and an increase in right sternocleidomastoid stiffness (p = 0.002), and a decrease in platysma elasticity (Right, p = 0.039; Left, p = 0.017). The change in CVA was found to have a negative correlation with the gamma activity (P7, p = 0.044; P8, p = 0.004). Therefore, increased gamma wave activity in FHP appears to be related to CVA decrease due to external force that was applied to the nervous system and cervical spine.

Jeong HJ, et al. J Clin Neurol. 2020 Apr;16(2):202-214. https://doi.org/10.3988/jcn.2020.16.2.202