In cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD), the amyloid ␤ (A␤) peptide deposits along the vascular lumen, leading to degeneration and dysfunction of surrounding tissues. Activated coagulation factor XIIIa (FXIIIa) covalently cross-links proteins in blood and vasculature, such as in blood clots and on the extracellular matrix. Although FXIIIa co-localizes with A␤ in CAA, the ability of FXIIIa to cross-link A␤ has not been demonstrated. Using Western blotting, kinetic assays, and microfluidic analyses, we show that FXIIIa covalently cross-links A␤40 into dimers and oligomers (k cat /K m ‫؍‬ 1.5 ؋ 10 5 M ؊1 s ؊1), as well as to fibrin, platelet proteins, and blood clots under flow in vitro. A␤40 also increased the stiffness of platelet-rich plasma clots in the presence of FXIIIa. These results suggest that FXIIIa-mediated cross-linking may contribute to the formation of A␤ deposits in CAA and Alzheimer's disease. Amyloid ␤ (A␤) 4 is a 4 kDa intrinsically disordered protein that accumulates along the cerebral vasculature during cerebral amyloid angiopathy (CAA). The accumulation of A␤ leads to the degeneration of surrounding cells and is associated with microhemorrhages (1). Although CAA is present in over 90% of patients with Alzheimer's disease (AD) (2), the mechanisms underlying A␤ deposition on blood vessels remains unclear.

Background: Our group previously developed an upper extremity repositioning (Sup-ER) protocol for brachial plexus birth injuries (BPBIs) that may improve supination and external rotation (ER) at 2 years of age. Questions were raised about the potential for the protocol to cause internal rotation (IR) deficits. The goal of this study was to explore the longer-term outcomes of the Sup-ER protocol and investigate IR/ER function. Methods: This prospective cross-sectional cohort study examined 16 children older than 4 years of age with significant enough BPBI to be treated with the Sup-ER protocol. Total shoulder and elbow function were assessed, including passive and active ranges of motion and strength of IR and ER. Results: Range of motion (ROM) for most active movements was decreased in the affected compared to unaffected arm. Notably, IR passive ROM was similar in the affected (78.7°) and unaffected arm (82.8°). External rotation strength of the affected arm was weaker (42.8 N) compared to the unaffected arm (57.9 N). IR strength had a greater deficit in the affected (43.2 N) arm compared to the unaffected arm (72.2 N), but both ER and IR showed less deficit than described in the literature. Conclusions: Despite differences in ranges of motion between the affected and unaffected arms, ROMs for the affected arm were comparable to the functional limits as reported in the literature. The Sup-ER protocol shows potential to optimize long-term shoulder rotation function in children with BPBI without compromising IR.

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