Browsing by Subject "Early‐onset Alzheimer's disease"

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    Neuropsychiatric symptom burden in early‐onset and late‐onset Alzheimer's disease as a function of age
    (Wiley, 2024) Polsinelli, Angelina J.; Johnson, Sierah; Crouch, Adele; Lane, Kathleen A.; Pena-Garcia, Alex; Hammers, Dustin B.; Wang, Sophia; Gao, Sujuan; Apostolova, Liana G.; Neurology, School of Medicine
    Introduction: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. Methods: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. Results: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). Discussion: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. Highlights: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.
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    Transcriptome analysis of early‐ and late‐onset Alzheimer's disease in Korean cohorts
    (Wiley, 2025) Han, Sang-Won; Hwang, Jiyun; Park, Tamina; Pyun, Jung-Min; Lee, Joo-Yeon; Park, Jeong Su; Bice, Paula J.; Liu, Shiwei; Yun, Sunmin; Jeong, Jibin; Risacher, Shannon L.; Saykin, Andrew J.; Byun, Min Soo; Yi, Dahyun; Sung, Joohon; Lee, Dong Young; Kim, Sang Yun; Nho, Kwangsik; Park, Young Ho; Radiology and Imaging Sciences, School of Medicine
    Introduction: The molecular mechanisms underlying early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations. Methods: RNA-sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co-expression network analysis. Findings were replicated in an independent Korean cohort (N = 275). Results: DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD-associated module showing a significant enrichment in pathways related to mitophagy, 5' adenosine monophosphate-activated protein kinase signaling, and ubiquitin-mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LOAD-associated module was highly preserved. In addition, SMOX and PLVAP were associated with brain amyloid beta deposition. Discussion: Our findings suggest distinct molecular signatures for EOAD and LOAD in a Korean population, providing deeper understanding of their diagnostic potential and molecular mechanisms. Highlights: Analysis identified 18 and 88 dysregulated genes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively. Expression levels of SMOX and PLVAP were downregulated in LOAD. Expression levels of SMOX and PLVAP were associated with brain amyloid beta deposition. Pathways including mitophagy and 5' adenosine monophosphate-activated protein kinase signaling were enriched in a LOAD module. A LOAD module was highly preserved across two independent cohorts.