Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries DOI Creative Commons
Xiaoyi Xu, Jennifer M. Kwon,

Ruixin Yan

et al.

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(3), P. e250562 - e250562

Published: March 11, 2025

Importance Age, sex, and apolipoprotein E ( APOE ) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of in AD varies with sex ancestry. While association biomarkers also across ancestry, no study has systematically investigated both sex-specific ancestry differences on cerebrospinal fluid (CSF) together, resulting limited insights generalizability. Objective To investigate -ε4 3 core CSF ancestries. Design, Setting, Participants This cohort examined (amyloid β1-42 [Aβ42], phosphorylated tau 181 [p-tau], total tau, participants from 20 cohorts July 1, 1985, to March 31, 2020. These individuals were grouped into African, Asian, European ancestries based genetic data. Data analyses conducted June 2023, November 10, 2024. Exposure Sex (male or female) -ε4. Main Outcomes Measures associations biomarker levels assessed within each group, adjusting age. Meta-analyses performed identify these Sensitivity exclude potential influence -ε2 allele. Results included 4592 (mean [SD] age, 70.8 [10.2] years; 2425 [52.8%] female; 119 [2.6%] 52 [1.1%] 4421 [96.3%] European). Higher dosage scores associated lower Aβ42 values (β [SE], −0.58 [0.02], P < .001), indicating more severe pathology; seen men women separately jointly. was statistically greater −0.63 [0.03]; .001) vs −0.52 = .01 interaction). Women had higher p-tau, neurofibrillary pathology. between p-tau expected direction (higher values) sexes, but difference sexes significant only those African 0.10 [0.18]; .57 men; β 0.66 [0.17]; .001 women; .03 neuronal damage. stronger than 0.20 [0.22]; .36 0.65 [0.22], .004 [ .16 interaction]) 0.36 0.27 [0.03], .053 interaction]); found Asian cohort. analysis excluding APOE- ε2 carriers yielded similar results. Conclusions Relevance In this study, allele accumulation men. findings underscore importance considering -ε4’s pathology mechanisms AD. Although provides robust evidence complex interplay further research is needed fully understand other differences.

Language: Английский

Single-cell sequencing to multi-omics: technologies and applications DOI Creative Commons
Xiangyu Wu, Xin Yang,

Yunhan Dai

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 27, 2024

Abstract Cells, as the fundamental units of life, contain multidimensional spatiotemporal information. Single-cell RNA sequencing (scRNA-seq) is revolutionizing biomedical science by analyzing cellular state and intercellular heterogeneity. Undoubtedly, single-cell transcriptomics has emerged one most vibrant research fields today. With optimization innovation technologies, intricate details concealed within cells are gradually unveiled. The combination scRNA-seq other multi-omics at forefront field. This involves simultaneously measuring various omics data individual cells, expanding our understanding across a broader spectrum dimensions. precisely captures aspects transcriptomes, immune repertoire, spatial information, temporal epitopes, in diverse contexts. In addition to depicting cell atlas normal or diseased tissues, it also provides cornerstone for studying differentiation development patterns, disease heterogeneity, drug resistance mechanisms, treatment strategies. Herein, we review traditional technologies outline latest advancements multi-omics. We summarize current status challenges applying biological clinical applications. Finally, discuss limitations potential strategies address them.

Language: Английский

Citations

21
Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases DOI Creative Commons
Anna Ungvari, Rafał Gulej, Roland Patai

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

3
Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics DOI

Sneh Prabha,

Mohd Sajad,

Gulam Mustafa Hasan

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102476 - 102476

Published: Aug. 31, 2024

Language: Английский

Citations

15
Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model DOI Creative Commons
Gillian Carling, Li Fan,

Nessa R. Foxe

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(23), P. 3877 - 3896.e8

Published: Sept. 30, 2024

The strongest risk factors for late-onset sporadic Alzheimer's disease (AD) include the ε4 allele of apolipoprotein E (APOE), R47H variant triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 TREM2

Language: Английский

Citations

12
The Link Between Matrix Metalloproteinases and Alzheimer’s Disease Pathophysiology DOI Creative Commons

Dominika Radošinská,

Jana Radošinská

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: June 27, 2024

Alzheimer's disease (AD) is a major contributor to dementia and the most common neurodegenerative disorder. In AD pathophysiology, matrix metalloproteinases (MMPs)-proteolytic enzymes, best known be responsible for remodeling degradation of extracellular matrix-were suggested play an important role. Due diverse nature published data frequent inconsistent results presented in available papers, it was considered essential analyze all aspects MMP literature with respect pathophysiology attempt outline unifying concept understanding their role AD. Thus, main contribution this review article summarize recent research on participation obtained using cell cultures understand molecular principles action. Furthermore, updated comprehensive view regarding topic based exclusively papers from human studies provided as well. It can concluded that determining exact any particular MMPs holds promise establishing potential biomarkers reflecting severity or progression developing new therapeutic agents targeting processes lead

Language: Английский

Citations

11
Mitochondrial dysfunction in Alzheimer’s disease: a key frontier for future targeted therapies DOI Creative Commons
Shuguang Wang, Zuning Liao, Qiying Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, accounting for approximately 70% of dementia cases worldwide. Patients gradually exhibit cognitive decline, such as memory loss, aphasia, and changes in personality behavior. Research has shown that mitochondrial dysfunction plays a critical role onset progression AD. Mitochondrial primarily leads to increased oxidative stress, imbalances dynamics, impaired mitophagy, genome abnormalities. These abnormalities are closely associated with amyloid-beta tau protein pathology, collectively accelerating process. This review summarizes mitochondria development AD, latest research progress, explores potential mitochondria-targeted therapeutic strategies Targeting mitochondria-related pathways may significantly improve quality life AD patients future.

Language: Английский

Citations

1
Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus DOI Creative Commons

Bianca Caroline Bobotis,

Mohammadparsa Khakpour,

Olivia Braniff

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 24, 2025

The brain presents various structural and functional sex differences, for which multiple factors are attributed: genetic, epigenetic, metabolic, hormonal. While biological is determined by both chromosomes hormones, little known about how these two interact to establish this dimorphism. Sex differences in the also affect its resident immune cells, microglia, actively survey parenchyma with hormones throughout life. However, microglial density distribution, morphology ultrastructural patterns physiological conditions during adulthood largely unknown. Here, we investigated aforementioned properties of microglia using Four Core Genotypes (FCG) model, allows an independent assessment gonadal chromosomal effects four conditions: FCG XX Tg XY− (both ovaries); XXSry XYSry testes). We compared results XY wild-type (WT) mice. In adult mice, focused our investigation on ventral hippocampus across different layers: CA1 stratum radiatum (Rad) lacunosum-moleculare (LMol), as well dentate gyrus polymorphic layer (PoDG). Double immunostaining Iba1 TMEM119 revealed that influenced hormones. show Rad LMol denser however, were densest WT PoDG, ovarian animals had increased testes animals. Additionally, was modulated a complex interaction between chromosomes, affecting their cellular soma arborization hippocampal layers. Moreover, analysis showed make overall more contacts pre- post-synaptic elements than Lastly, markers stress, including mitochondrion elongation, dilation endoplasmic reticulum Golgi apparatus, mostly chromosomally driven. Overall, characterized aspects normal found be shaped shading light onto immunity at steady-state.

Language: Английский

Citations

1
Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease DOI Creative Commons
Gillian Coughlan,

Zoe B. Rubinstein,

Hannah M Klinger

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(10)

Published: March 5, 2025

Elucidating the downstream impact of exogenous hormones on aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET N = 146 baseline clinically normal women, aged 51 89 years. Women were scanned a 4.5-year (SD, 2.1; range, 1.3 10.4) 3.5-year 1.5; 1.2 8.1) period Aβ tau, respectively, ~14 years after initiation HT. In older (aged >70 years), HT users exhibited faster regional relative non-users, localized entorhinal cortex inferior temporal fusiform gyri, an indirect effect cognitive decline through accumulation. younger <70 associations negligible. Findings are relevant optimizing treatment guidelines.

Language: Английский

Citations

1
Emerging role of macrophages in neuropathic pain DOI Creative Commons

Sihan Tong,

Delin Liu, Peng Liao

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 227 - 241

Published: March 1, 2025

Language: Английский

Citations

1
Global, Regional, and National Burden of Early‐Onset Alzheimer's Disease and Other Dementias in Young Adults Aged 40–64 Years, 1990–2021: A Population‐Based Study DOI Creative Commons

Zenghui Zhang,

Shaojie Han, Huimin Zhu

et al.

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(3)

Published: March 1, 2025

ABSTRACT Background and Purpose Early‐onset Alzheimer's disease other dementias (EOAD) impose significant burdens on affected individuals their families. However, the global burden of EOAD has not been fully investigated. We aimed to assess global, regional, national using data from Global Burden Diseases, Injuries, Risk Factors (GBD) study 1990 2021. Methods Data for adults aged 40–64 were extracted within GBD 2021 framework. Primary outcomes included age‐standardized prevalence, incidence, mortality, disability‐adjusted life years (DALYs) EOAD, as well average annual percentage change (AAPC) across 21 regions 204 countries. Results In 2021, cases reached 7.75 million (95% uncertainty interval [UI] 5.82–10.08), up 3.67 UI 2.75–4.76) in 1990. The prevalence rate increased 341.2 per 100,000 255.89–442.79) 363.5 with an AAPC 0.26% ( p < 0.001). was higher women than men (4.28 million, 95% 3.24–5.56, vs. 3.46 2.57–4.52). associated 0.07 0.01–0.23) deaths 3.77 1.69–8.88) DALYs Additionally, 1.06 0.07–3.03) attributable smoking, elevated fasting plasma glucose, high body mass index. Conclusions number among more doubled Targeted strategies interventions are urgently needed address this growing public health issue.

Language: Английский

Citations

1