Mapping the functional topology from a multifaceted perspective and relating it to underlying cross-scale structural principles is crucial for understanding the structural-functional relationships of the cerebral cortex. Previous works have described a sensory-association gradient axis in terms of coupling relationships between structure and function, but largely based on single specific feature, and the mesoscopic underpinnings are rarely determined. Here we show a gradient pattern encoded in a functional similarity network based on data from Human Connectome Project and further link it to cytoarchitectonic organizing principles. The spatial distribution of the primary gradient follows an inferior-anterior to superior-posterior axis. The primary gradient demonstrates converging relationships with layer-specific microscopic gene expression and mesoscopic cortical layer thickness, and is captured by the geometric representation of a myelo- and cyto-architecture based laminar differentiation theorem, involving a dual origin theory. Together, these findings provide a gradient, which describes the functional topology, and more importantly, linking the macroscale functional landscape with mesoscale laminar differentiation principles.
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http://dx.doi.org/10.1038/s42003-022-04148-4 | DOI Listing |
Background: Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical studies (phase 2, NCT01767311 and phase 3 ClarityAD, NCT03887455) in early Alzheimer's disease, lecanemab substantially reduced amyloid PET and significantly slowed clinical decline on multiple measures of cognition and function, including CDR-SB at 18 months. Models describing the change in amyloid PET and CDR-SB in response to lecanemab treatment were used to explore the impact of changing from the initial dosage regimen (10 mg/kg every 2 weeks [Q2W]) to a less intensive maintenance dosing regimen (10 mg/kg every 4 weeks [Q4W]) on clinical efficacy, and to explore the optimal duration of the initial dosing regimen.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China.
Background: Effective early intervention of mild cognitive impairment (MCI) is the key for preventing dementia. However, there is currently no drug for MCI. As a multi-targeted neuroprotective agent, butylphthalide has been demonstrated to repair cognition in patients with vascular cognitive impairment, and has the potential to treat MCI due to Alzheimer's disease (AD).
View Article and Find Full Text PDFBackground: Genetic studies have established that loss of function SORL1 gene variants are associated with Alzheimer's disease (AD). SORL1 encodes an endosomal trafficking receptor, SORLA, which regulates endosomal protein recycling through its interaction with the retromer core complex (consisting of VPS26, VPS35 and VPS29). Deficits in the levels and function of the SORLA-retromer complex are thought to underlie AD.
View Article and Find Full Text PDFHistol Histopathol
December 2024
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Sex hormones regulate gut function and mucosal immunity; however, their specific effects on the mucosa-associated lymphoid tissue (MALT) in the rectum of mammals remain unclear. Here, we aimed to investigate the influence of sex on MALT in the rectum of mammals by focusing on the rectal mucosa-associated lymphoid tissues (RMALTs) of C57BL/6NCrSIc mice. Histological analysis revealed that RMALTs were predominantly located in the lamina propria and submucosa of the rectal mucosa, with a significant sex-related difference in the distance from the anorectal junction to the first appearance of the RMALT.
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