Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice

Heparan sulfate accumulation with Abeta deposits in Alzheimer's disease and Tg2576 mice is contributed by glial cells.

Contains fulltext : 70077.pdf (Publisher’s version ) (Closed access)Amyloid beta-peptide (Abeta) plaques, one of the major neuropathological lesions in Alzheimer's disease (AD), can be broadly subdivided into two morphological categories: neuritic and diffuse. Heparan sulfate (HS) and HS proteoglycans (HSPGs) are codeposits of multiple amyloidoses, including AD. Although HS has been considered a limiting factor in the initiation of amyloid deposition, the pathological implications of HS in Abeta deposits of AD remain unclear. In this study, immunohistochemistry combined with fluorescence and confocal microscopy was employed to gain deeper insight into the accumulation of HS with Abeta plaques in sporadic and familial AD. Here we demonstrate that HS preferentially accumulated around the Abeta40 dense cores of neuritic plaques, but was largely absent from diffuse Abeta42 plaques, suggesting that Abeta42 deposition may occur independently of HS. A codeposition pattern of HS with Abeta deposits in Tg2576 mice was also examined. We identified the membrane-bound HSPGs, glypican-1 (GPC1) and syndecan-3 (SDC3), in glial cells associated with Abeta deposits, proximal to sites of HS accumulation. In mouse primary glial cultures, we observed increased levels of GPC1 and SDC3 following Abeta stimulation. These results suggest that HS codeposits with Abeta40 in neuritic plaques and is mainly derived from glial cells

The AAPM/ASTRO 2023 Core Physics Curriculum for Radiation Oncology Residents

Purpose: The American Association of Physicists in Medicine Radiation Oncology Medical Physics Education Subcommittee (ROMPES) has updated the radiation oncology physics core curriculum for medical residents in the radiation oncology specialty. Methods and Materials: Thirteen physicists from the United States and Canada involved in radiation oncology resident education were recruited to ROMPES. The group included doctorates and master's of physicists with a range of clinical or academic roles. Radiation oncology physician and resident representatives were also consulted in the development of this curriculum. In addition to modernizing the material to include new technology, the updated curriculum is consistent with the format of the American Board of Radiology Physics Study Guide Working Group to promote concordance between current resident educational guidelines and examination preparation guidelines. Results: The revised core curriculum recommends 56 hours of didactic education like the 2015 curriculum but was restructured to provide resident education that facilitates best clinical practice and scientific advancement in radiation oncology. The reference list, glossary, and practical modules were reviewed and updated to include recent literature and clinical practice examples. Conclusions: ROMPES has updated the core physics curriculum for radiation oncology residents. In addition to providing a comprehensive curriculum to promote best practice for radiation oncology practitioners, the updated curriculum aligns with recommendations from the American Board of Radiology Physics Study Guide Working Group. New technology has been integrated into the curriculum. The updated curriculum provides a framework to appropriately cover the educational topics for radiation oncology residents in preparation for their subsequent career development. (c) 2023 Elsevier Inc. All rights reserved