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Drug Development.

Alzheimers Dement

December 2024

ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).

Background: The Apolipoprotein E4 isoform (ApoE4), encoded by the APOE gene, stands out as the most influential genetic factor in late-onset Alzheimer's disease (LOAD). The ApoE4 isoform contributes to metabolic and neuropathological abnormalities during brain aging, with a strong correlation observed in APOE4-positive Alzheimer's disease cases between phosphorylated tau burden and amyloid deposition. Despite compelling evidence of APOE-mediated neuroinflammation influencing the progression of tau-mediated neurodegeneration, the molecular mechanisms underlying these phenomena remain largely unknown.

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Background: Early-onset Alzheimer's disease (EOAD) associated with amyloid precursor protein (APP) duplications or presenilin (PSEN) variants increases risk of seizures. Targeting epileptiform activity with antiseizure medicine (ASM) administration to AD patients may beneficially attenuate cognitive decline (Vossel et al, JAMA Neurology 2021). However, whether mechanistically distinct ASMs differentially suppress seizures in discrete EOAD models is understudied (Lehmann et al, Neurochem Res 2021).

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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

Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.

Background: A traditional method for validating a surrogate endpoint typically involves assessing the correlation between changes in biomarkers and changes in clinical endpoints using Pearson's and/or Spearman's correlation. However, this approach may not provide an accurate representation of the true correlation due to several reasons: (i) it only considers the change from baseline to the last visit and does not use all post-baseline longitudinal data; (ii) the raw change has large variability; (iii) it does remove the within-subject variability. The objective of this presentation is to propose two alternative approaches that overcome these limitations and allow for a more accurate estimation of the true correlation using all available longitudinal data.

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Dementia Care Research and Psychosocial Factors.

Alzheimers Dement

December 2024

7072 mulago hill, Kampala, Uganda.

Background: In Uganda, caregivers of Alzheimer's disease and related dementias (ADRD) face complex challenges, often lacking specialized skills for effective caregiving. Despite the growing prevalence of ADRD in the country, there's a significant literature gap on caregiver selection and obstacles faced in urban and rural areas. This study aims to provide insights into the experiences of Ugandan caregivers, enhancing understanding of ADRD caregiving.

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