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Interplay of age-sensitive cortical vulnerability and dopaminergic degeneration in clinical manifestations of Parkinson's disease

2026-07-01T00:00:00Z

Title: Interplay of age-sensitive cortical vulnerability and dopaminergic degeneration in clinical manifestations of Parkinson's disease Authors: Kang, Sungwoo; Na, Han Kyu; Yoon, So Hoon; Kim, Han-Kyeol; Ryu, Young Hoon; Lee, Hye Sun; Yoo, Han Soo; Lyoo, Chul Hyoung; 유한수 Abstract: To identify the pattern of cortical atrophy variation in Parkinson's disease (PD) and its contribution to clinical manifestations beyond dopaminergic dysfunction, 45 healthy controls (HCs) underwent MRI, and 222 participants with PD additionally underwent dopamine transporter (DAT)-PET, Unified PD Rating Scale (UPDRS), and neuropsychological tests. Using principal component analysis in PD, a single pattern in cortical thickness (PC1PD) was identified. Linear regressions models were applied to investigate the effects of PC1PD and putaminal DAT (DAT-P) on parkinsonism, and PC1PD and caudate DAT (DAT-C) on cognition. PC1PD accounted for more than 80% of total cortical variance and showed a strong negative correlation with age. The spatial pattern of PC1PD was similar to that of PC1 derived from HCs, but its age-related association was more pronounced in PD. Independent of DAT-P, lower PC1PD was associated with higher UPDRS motor score and showed a synergistic significant interaction with DAT-P on the axial subscore. Independent of DAT-C, lower PC1PD was associated with worse performance in global cognition, language, and executive functions, with synergistic interaction with DATC on global cognition and executive function. The associations of PC1PD with UPDRS motor scores, general cognition, and executive function were stronger in older participants, indicating that aging amplifies the clinical effect of PC1PD. PC1PD represents an age-sensitive cortical vulnerability axis whose expression is amplified in PD, and its interplay with dopaminergic depletion and aging contributes to axial motor symptoms and executive dysfunction in PD.

Association of body composition and nutritional status with survival in stage IV colorectal cancer patients who underwent resection: a retrospective cohort study

2026-03-01T00:00:00Z

Title: Association of body composition and nutritional status with survival in stage IV colorectal cancer patients who underwent resection: a retrospective cohort study Authors: Lee, Jae Won; Lee, Jae-Hoon; Cho, Eun-Suk; Shin, Su-Jin; Lee, Hye Sun; Lee, Kang Young; Kang, Jeonghyun Abstract: Purpose: Although host body composition, nutritional and systemic inflammatory status have been suggested to have an impact on prognosis in patients with colorectal cancer (CRC), their impact on patients with stage IV CRC remains unclear. This study investigated the prognostic effects of those parameters in patients initially diagnosed with stage IV CRC who underwent surgery. Methods: Patients with stage IV CRC who underwent surgery were selected. Preoperative computed tomography images were evaluated for skeletal muscle index, skeletal muscle density (SMD), visceral fat area (VFA), and subcutaneous fat area (SFA). For nutritional status and systemic inflammation, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were used. The Cox proportional hazard model was used to evaluate the prognostic significance of progression-free survival (PFS) after adjustment for the other covariates in the model. Results: Data of 134 patients with stage IV CRC who underwent surgery between January 2005 and February 2014 were included. SMD, VFA, SFA, PNI, NLR, LMR, and PLR were associated with PFS in the univariable analysis. In the multivariable analysis, SFA (hazard ratio [HR], 0.612; 95% confidence interval [CI], 0.389-0.961; P = 0.033), and PNI (HR, 0.536; 95% CI, 0.345-0.832; P = 0.005) were identified to be independent prognostic factors for PFS. Conclusion: SFA and PNI both demonstrated prognostic significance in patients with stage IV CRC. Accordingly, we believe further studies are warranted to determine whether incorporating these factors can aid in surgical decision-making for stage IV CRC patients.

Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus

2026-02-01T00:00:00Z

Title: Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus Authors: Kang, Chan Woo; Hong, Zhen-Yu; Oh, Ju Hun; Farh, Mohamed El-Agamy; Wang, Eun Kyung; Lee, Soohyun; Kang, Un Ho; Nam, Jung Ho; Lee, Yang Jong; Shin, Hyeju; Kim, Ye Bin; Jeon, Hyeonuk; Jeong, Jae Woong; Kim, Doyeon; Kim, Jung Seung; Hong, Seung Soo; Park, Jong-Pil; Cho, Hyo Je; Fang, Sungsoon; Kim, Hyongbum Henry; Cho, Arthur; Lim, Byung Kook; Sohn, Insuk; Ku, Cheol Ryong; 홍승수; 구철룡 Abstract: Intestinal glucose excretion, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycaemic control. Here, we investigate molecular mechanisms that activate intestinal glucose excretion. We evaluate altered transcriptomes in variable intestinal glucose excretion models and big data-based drug discovery systems. We show that protein kinase C (PKC) activation mimics transcriptome alterations observed during intestinal glucose excretion. Among PKC subfamilies, atypical PKC (aPKC) facilitates glucose transporter 1 (GLUT1)-mediated intestinal glucose excretion without inducing oncogenic proliferation. Intestinal aPKC activation via transposon expression vector induces serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activates aPKC and induces a similar effect on intestinal glucose excretion. We identify the prostratin and aPKC/GLUT1 signalling pathways as putative targets for treating diabetes, providing insights into the future development of antidiabetic and weight-loss drugs.

Plasma p-tau217 predicts PET-based pathological staging for precision Alzheimer disease assessment

2026-02-01T00:00:00Z

Title: Plasma p-tau217 predicts PET-based pathological staging for precision Alzheimer disease assessment Authors: Kim, Han-Kyeol; Lee, Jae Hoon; Chun, Joong-Hyun; Kim, You Jin; Park, Mina; West, Tim; Kirmess, Kristopher M.; Verghese, Philip B.; Connell, Daniel; Braunstein, Joel B.; Ryu, Young Hoon; Cho, Hanna; Lyoo, Chul Hyoung Abstract: INTRODUCTION: While positron emission tomography (PET) is the standard for pathological staging, its limited availability necessitates accessible alternatives. We evaluated plasma biomarkers for detecting PET-based stages using single-axis (Thal/Braak) and integrated A/T composite models. METHODS: We enrolled 237 AD spectrum participants undergoing multimodal assessments including amyloid/tau PET and plasma biomarker analysis (phosphorylated tau [p-tau] 217, %p-tau217, and amyloid beta [A beta] 42/40 ratio). Detecting and discriminative performance was assessed using receiver operating characteristics (ROC) analysis and probability-based stage prediction. RESULTS: Plasma p-tau217-based biomarkers showed excellent detecting performance for early amyloid (Thal I-II; area under the curve values > 0.96) and intermediate tau (Braak III-IV; area under the curve values > 0.92). Probability-based prediction identified therapeutic window thresholds of 1.895-5.077 pg/mL. Notably, integrated A/T composite staging yielded highly consistent thresholds (< 3% variance). DISCUSSION: Plasma p-tau217-based biomarkers accurately reflect PET-based staging across frameworks. The convergent therapeutic window thresholds demonstrate robust biological transitions, enabling accessible identification of optimal candidates for disease-modifying therapies. Highlights center dot Plasma phosphorylated tau (p-tau) 217 and %p-tau217 were directly aligned with positron emission tomography (PET)-defined Alzheimer's disease pathology using both single-axis staging (amyloid Thal phases, tau Braak stages) and integrated A/T composite staging. center dot Plasma p-tau217-based biomarkers consistently outperformed the amyloid beta (A beta) 42/40 ratio, showing excellent discrimination for early amyloid pathology and intermediate tau burden across PET-based staging frameworks. center dot Probability-based modeling defined stage-specific operating points, including optimal cutoffs and 50% probability thresholds, revealing a convergent biomarkerdefined therapeutic window across single-axis and composite staging approaches. center dot These findings support a plasma-first pathological staging strategy to identify treatment-eligible patients and prioritize confirmatory PET, particularly in clinical settings with limited imaging availability.