Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AβO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AβOs from both monomeric and fibrillar Aβ. NUsc1 readily detected AβOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AβO binding and reduced AβO-induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD-transgenic mice from wild type (WT) mice, and detected endogenous AβOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AβOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AβO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics.

Background: The increasing trend of women with unilateral breast cancer to electively undergo contralateral prophylactic mastectomy in addition to treatment of the index breast has been controversial. The authors set out to better frame the risks and benefits of contralateral prophylactic mastectomy in the treatment of unilateral breast cancer by evaluating outcomes of a large, consecutive cohort of patients. Methods: An institutional review board–approved review of a single-surgeon (N.T.) experience (2013 to 2018) was conducted of all consecutive patients with unilateral breast cancer treated with mastectomy and immediate reconstruction. Patient characteristics, surgical pathologic results, and 30-day complications were assessed. Outcomes of patients with unilateral cancer who underwent unilateral mastectomy versus bilateral mastectomy (with one breast being contralateral prophylactic mastectomy) were compared. Logistic regression models evaluated various risk factors for potential associations with positive pathologic findings in the contralateral prophylactic mastectomy specimen and/or postoperative complications. Results: Of 244 patients, 68 (27.9 percent) underwent unilateral mastectomy and 176 (72.1 percent) underwent contralateral prophylactic mastectomy. Surgical pathologic results of the prophylactic breast revealed occult ductal carcinoma in situ or invasive cancer in 13 patients (7.3 percent) and lobular carcinoma in situ in eight patients (4.6 percent). Incidence of complications was similar between groups [unilateral mastectomy, 19.12 percent (n = 13); contralateral prophylactic mastectomy, 13.07 percent (n = 23); p = 0.234]. Conclusions: Immediate reconstruction for unilateral mastectomy and contralateral prophylactic mastectomy have similar complication risk profiles, among patients as a whole and between individual breasts. These findings contribute to our understanding of the clinical impact prophylactic mastectomy and reconstruction may have on optimizing the counseling among extirpative surgeons, reconstructive surgeons, and patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.