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Drug Development.

Alzheimers Dement

December 2024

Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, Netherlands.

The lack of an in-vivo pathology marker for synuclein pathology has been a long standing challenge for dementia for Lewy bodies (DLB) research. This issue is critically important for phase II trials, which are often small, requiring the precise measurement of the biological effects, whether disease modifying or symptomatic. Recent advances have enabled the determination of alpha-synuclein pathology status with CSF measurements, using aggregation assays [RT-QUIC].

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Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.

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Drug Development.

Alzheimers Dement

December 2024

University of Southern California, San Diego, USA.

Background: Recruitment of demographically diverse participants into Alzheimer's disease (AD) clinical trials, encompassing both screening and randomization, remains a consistent and persistent challenge contributing to underrepresentation of certain groups. Despite the exciting prospects of identifying therapeutic interventions for biomarker-eligible, cognitively unimpaired individuals, these studies grapple with the inherent complexities of AD trials coupled with intricate and time-consuming screening processes. Addressing this the issue of underrepresentation necessitates concerted and intentional efforts that prioritize inclusivity and equitable access to enroll adults meeting study criteria, reflecting the demographic and social diversity of North America.

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Sex-related differences in the morphology of rectal mucosa-associated lymphoid tissues in C57BL/6NCrSlc mice.

Histol 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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Drug Development.

Alzheimers Dement

December 2024

Deakin University, Geelong, VIC, Australia.

Background: Reliable treatment approaches for addressing early cognitive impairment and Alzheimer's disease (AD) are currently lacking. Given the multifactorial nature of AD, therapeutic strategies need to focus on disease-specific biochemical pathways. Given the significance of metabolic pathways in cognitive impairment, it is essential to investigate alternative disease modifiers capable of targeting multiple metabolic pathways, such as phytochemicals.

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