Tau interacts with SHP2 in neuronal systems and in Alzheimer's disease brains.

Microtubule-associated protein tau, an integral component of neurofibrillary tangles, interacts with a variety of signaling molecules. Previously, our laboratory reported that nerve growth factor (NGF)-induced MAPK activation in a PC12-derived cell line was potentiated by tau, with phosphorylation at T231 being required. Therefore, we sought to identify a signaling molecule involved in the NGF-induced Ras-MAPK pathway that interacted with phospho-T231-tau. Here, we report that the protein tyrosine phosphatase SHP2 (also known as PTPN11) interacted with tau, with phospho-T231 significantly enhancing the interaction. By using proximity ligation assays, we found that endogenous tau-SHP2 complexes were present in neuronal cells, where the number of tau-SHP2 complexes significantly increased when the cells were treated with NGF, with phosphorylation at T231 being required for the increase. The interaction did not require microtubule association, and an association between tau and activated SHP2 was also found. Tau-SHP2 complexes were also found in both primary mouse hippocampal cultures and adult mouse brain. Finally, SHP2 levels were upregulated in samples from patients with mild and severe Alzheimer's disease (AD), and the level of tau-SHP2 complexes were increased in AD patient samples. These findings strongly suggest a role for the tau-SHP2 interaction in NGF-stimulated neuronal development and in AD.This article has an associated First Person interview with the first author of the paper.

Chronic distal biceps avulsion treated with suture button.

BACKGROUND: Distal biceps tendon avulsions account for 3%-10% of all biceps ruptures. Treated nonoperatively, these injuries lead to a loss of endurance, supination strength, and flexion strength compared with operative repair or reconstruction. Operative management of chronic injury has classically been with graft tissue to augment the contracted muscle. We present our results for chronic distal biceps avulsions secured with suture button through a single transverse incision in high flexion without the need for allograft augmentation. MATERIALS AND METHODS: This was a retrospective review of 20 patients with 21 injuries who underwent primary surgical repair of chronic distal biceps tendon avulsions at an average of 10 weeks (range 4-42 weeks). All patients were treated with a single transverse incision with a suture button armed with nonabsorbable no. 2 core sutures. Postoperatively patients were found to have 50°-90° flexion contracture. All patients were placed in a simple sling postoperatively with gentle extension to gravity as tolerated immediately and no formal physical therapy. Patients were surveyed regarding pre- and postoperative American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, visual analog scale (VAS) score, Mayo Elbow Performance Score (MEPS), Oxford Elbow Score (OES), and overall satisfaction. Range of motion (ROM), flexion, and supination strength compared to the contralateral uninjured extremity were evaluated at final follow-up. RESULTS: Mean clinical follow-up was 26 months. All patients regained full ROM and 5/5 flexion and supination strength at final follow-up. MEPSs were 100 for all responding patients compared with an average 47.5 preoperatively (P < .0001). The mean postoperative ASES score was 97.2 compared with 41.9 preoperatively (P < .0001). Mean OESs pre- and postoperatively were 24.2 and 48, respectively (P < .0001). The mean VAS score was 4.4 preoperatively and was reported as 0 by all patients at final follow-up (P < .0001). Two patients had transient sensory radial nerve neuropathy, and 1 patient has persistent palsy. No synostoses occurred. Four patients reported supination fatigue postoperatively compared with the uninjured extremity. CONCLUSION: Given these results, we feel that chronic distal biceps tendon ruptures can be repaired successfully with a single incision using suture button technique without the use of a graft. Though the flexion contracture is significant postoperatively, all patients regained full ROM and had excellent postoperative functional outcome scores.