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Genetic variants in the apolipoprotein E ( APOE ) gene affect the onset and progression of Alzheimer's disease (AD). The APOE Christchurch ( APOE Ch) variant has been identified as the most prominent candidate for preventing the onset and progression of AD. In this study, we generated isogenic APOE3 Ch/ 3 Ch human-induced pluripotent stem cells (iPSCs) from APOE3 / 3 healthy control female iPSCs and induced them into astrocytes. RNA expression analysis revealed the inherent resilience of APOE3 Ch/ 3 Ch astrocytes to induce a reactive state in response to inflammatory cytokines. Moreover, cytokine treatment changed astrocytic morphology with more complexity in APOE3 / 3 astrocytes, but not in APOE3 Ch/ 3 Ch astrocytes, indicating resilience of the rare variant to a reactive state. Interestingly, we observed robust morphological alterations containing more intricate processes when cocultured with iPSC-derived cortical neurons, in which APOE3 Ch/ 3 Ch astrocytes reduced complexity compared with APOE3 / 3 astrocytes. To assess the impacts of tau propagation effects, we next developed a sophisticated and sensitive assay utilizing cortical neurons derived from human iPSCs, previously generated from donors of both sexes. We showed that APOE3 Ch/ 3 Ch astrocytes effectively mitigated tau propagation within iPSC-derived neurons. This study provides important experimental evidence of the characteristic functions exhibited by APOE3Ch/3Ch astrocytes, thereby offering valuable insights for the advancement of novel clinical interventions in AD research., Competing Interests: H.O. is a scientific consultant for SanBio and K Pharma. The other authors declare no competing financial interests., (Copyright © 2024 the authors.)

We aimed to identify prognostic factors of cancer-specific survival (CSS) in non-metastatic castration-resistant prostate cancer (M0CRPC) patients. The final analysis of this retrospective cohort included 82 patients who were diagnosed as M0CRPC between 1998 and 2018 at the University of Tokyo Hospital. CRPC was defined as prostate-specific antigen (PSA) progression (increased PSA ≥ 25% and ≥ 2 ng/mL above the nadir or detection of a metastatic lesion). The median value of age and PSA at the time of CRPC were 76 (range 55-94) years and 2.84 (range 2.04-22.5) ng/mL, respectively. The median follow-up time from CRPC diagnosis was 38 (range 3-188) months. The prognostic factors of CSS were 'PSA doubling time (PSADT) ≤ 3 months', 'time to CRPC diagnosis from the start of androgen deprivation therapy (TTCRPC) ≤ 12 months', of which TTCRPC was a novel risk factor of CSS. In the multivariate analysis, 'PSADT ≤ 3 months' and TTCRPC ≤ 12 months' remained as statistically significant predictors of CSS. Novel risk stratification was developed based on the number of these risk factors. The high-risk group showed a hazard ratio of 4.416 (95% confidence interval 1.701-11.47, C-index = 0.727)., (© 2022. The Author(s).)

Massive deposition of amyloid β peptides (Aβ) as senile plaques (SP) characterizes the brain pathology of Alzheimer's disease (AD). SPs exhibit a variety of morphologies, although little is known about the SP components that determine their morphology. Collagenous Alzheimer amyloid plaque component (CLAC) is one of the major non-Aβ proteinaceous components of SP amyloid in AD brains. Here we show that overexpression of CLAC precursor (CLAC-P) in the brains of APP transgenic mice results in a significant remodeling of amyloid pathology, i.e., reduction in diffuse-type amyloid plaques and an increase in compact plaques laden with thioflavin S-positive amyloid cores. In vivo microdialysis revealed a significant decrease in Aβ in the brain interstitial fluid of CLAC-P/APP double transgenic mice compared with APP transgenic mice. These findings implicate CLAC in the compaction of Aβ in amyloid plaques and the brain dynamics of Aβ.