ABSTRACT
The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated ß-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of ß-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.
Subject(s)
Alzheimer Disease , Animals , Humans , Mice , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Stem Cell Transplantation/adverse effects , Iatrogenic Disease , Mice, Transgenic , Disease Models, AnimalABSTRACT
BACKGROUND: Cervical musculoskeletal and neuromuscular attributes, which may vary between men and women, influence an individual's capacity to stabilize the head. OBJECTIVES: To examine sex differences in cervical musculoskeletal and neuromuscular attributes and their impact on head stability. The secondary objective was to examine the effects of anticipation and preload on head kinematics. METHODS: Thirty-four (20 men, 14 women) recreationally active adult athletes completed a perturbation protocol with anticipation and preloading conditions in this descriptive cross-sectional study. We assessed the neuromuscular response of the sternocleidomastoid to perturbation and head kinematics. We measured neck girth, sternocleidomastoid physiological cross-sectional area, and isometric strength. RESULTS: Women had smaller neck girth, smaller sternocleidomastoid physiological cross-sectional area, and lower isometric strength than men. Women had greater baseline electromyography (EMG) amplitude and greater peak EMG response than men. There were no sex differences in sternocleidomastoid onset latency or head kinematics. Women had a greater increase in baseline EMG amplitude after preloading and anticipated conditions. Preloading attenuated sex differences in muscle onset latency. Across the sexes, there was a significant main effect of anticipation on head kinematics. CONCLUSION: Men and women used different strategies to stabilize the head, and responded differently to the preloading and anticipation conditions. J Orthop Sports Phys Ther 2019;49(11):779-786. Epub 15 May 2019. doi:10.2519/jospt.2019.8760.
