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There is increasing evidence for the crucial role of metals in the pathology of Alzheimer's disease. Both the aggregation and neurotoxicity of beta amyloid are dependent on the presence of copper. This study investigated the ability of the copper-complexing drug tetrathiomolybdate to reduce beta amyloid pathology and spatial memory impairment in both a prevention and a treatment paradigm in the Tg2576 mouse model of Alzheimer's disease. Tetrathiomolybdate treatment lowered brain copper and reduced beta amyloid levels in the prevention paradigm, but not in the treatment paradigm. Our data suggests that controlled lowering of systemic copper may achieve anti-amyloid effects if initiated early in the disease process.

Object The ideal surgical management of high-grade spondylolisthesis remains unclear. Concerns regarding the original Bohlman transsacral interbody fusion technique with stand-alone autologous fibular strut include late graft fracture and incomplete reduction of lumbosacral kyphosis. The authors' goal was to evaluate the radiographic and surgical outcomes of patients treated for high-grade spondylolisthesis with either transsacral S-1 screws or standard pedicle screw fixation augmenting the Bohlman posterior transsacral interbody fusion technique. Methods A retrospective review of patients who underwent fusion for high-grade spondylolisthesis in which a Bohlman oblique posterior interbody fusion augmented with either transsacral or standard pedicle screw fixation was performed by 4 spine surgeons was completed. Estimated blood loss, operating time, perioperative complications, and need for revision surgery were evaluated. Upright pre- and postsurgical lumbar spine radiographs were compared for slip percent and slip angle. Results Sixteen patients (12 female and 4 male) with an average age of 29 years (range 9–66 years) were evaluated. The average clinical follow-up was 78 months (range 5–137 months) and the average radiographic follow-up was 48 months (range 5–108 months). Ten L4–S1 and 6 L5–S1 fusions were performed. Five fibular struts and 11 titanium mesh cages were used for interbody fusion. Six patients had isolated transsacral screws placed, with 2 (33%) of the 6 requiring revision surgery for nonunion. No nonunions were observed in patients undergoing spanning pedicle screw fixation augmenting the interbody graft. Six patients experienced perioperative complications including 3 iliac crest site infections, 1 L-5 radiculopathy without motor involvement, 1 deep vein thrombosis, and 1 epidural hematoma requiring irrigation and debridement. The average estimated blood loss and operating times were 763 ml and 360 minutes, respectively. Slip percent improved from an average of 62% to 37% (n = 16; p < 0.01) and slip angle improved from an average of 18° to 8° (n = 16; p < 0.01). No patient experienced L-5 or other motor deficit postoperatively. Conclusions The modified Bohlman technique for treatment of high-grade spondylolisthesis has reproducible outcomes among multiple surgeons and results in significant improvements in slip percent and slip angle. Fusion rates were high (14 of 16; 88%), especially with spanning instrumentation augmenting the oblique interbody fusion. Rates of L-5 motor deficit were low in comparison with techniques involving reduction of the anterolisthesis.

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.