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Unveiling Aging and Alzheimer's Disease-Associated Dynamics of LINE1 DNA Content and Protein Expression in Mouse Brains
Despite the long interspersed nuclear element-1 (LINE1, L1) retrotransposons having been implicated in Alzheimer's disease (AD), a fundamental understanding of the AD-specific lifespan-long trajectory of L1 has been limited. Here, we characterize the content and expression of L1 covering four brain regions (hippocampus, prefrontal cortex, cerebellum, and the rest of brain tissue) of APP/PS1 mice, a murine model of AD, and their wild-type C57BL/6 littermates from 3 to 24 months of age. We report...
Spatial Transcriptomic Characteristics of the Aging Human Ovary
Ovarian aging is a complex process that compromises fertility and elevates the risk of reproductive disorders. To elucidate its spatiotemporal dynamics, we integrated single-nucleus RNA sequencing and spatial transcriptomics to construct a comprehensive aging atlas of 12 human ovarian tissues spanning ages 12-54 (prepubertal, age 12, n = 1; young, ages 23-29, n = 4; middle-aged, ages 32-34, n = 2; and older-aged, ages 42-54, n = 5). Our analysis revealed aging-related transcriptomic shifts,...
Unveiling Aging and Alzheimer's Disease-Associated Dynamics of LINE1 DNA Content and Protein Expression in Mouse Brains
Despite the long interspersed nuclear element-1 (LINE1, L1) retrotransposons having been implicated in Alzheimer's disease (AD), a fundamental understanding of the AD-specific lifespan-long trajectory of L1 has been limited. Here, we characterize the content and expression of L1 covering four brain regions (hippocampus, prefrontal cortex, cerebellum, and the rest of brain tissue) of APP/PS1 mice, a murine model of AD, and their wild-type C57BL/6 littermates from 3 to 24 months of age. We report...
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<sup>1</sup>H-MR spectroscopy biomarkers are associated with plasma-derived biomarkers of amyloid-β and tau in the early phase of AD continuum
The objective of the study was to evaluate the relationship of plasma biomarkers of Alzheimer's disease (AD) with in vivo proton magnetic resonance spectroscopy (¹H-MRS) markers, and their association with cognitive function across the early stages of the AD continuum. Determining these associations may clarify the AD-related biological pathways and support the development of integrated AD blood and ¹H-MRS biomarkers for early detection of these pathways. Fifty-five older adults (40 cognitively...
Depressive symptoms and plasma AT(N) biomarkers among cognitively healthy and mild cognitively impaired in a diverse cohort
Depression is a known risk factor for dementia and MCI, but its associations with AT(N) biomarkers remain inconsistent and may differ by cognitive status. We cross-sectionally studied 2929 dementia-free participants from the Health & Aging Brain Study-Health Disparities (HABS-HD). Mild cognitive impairment (MCI) was identified as having cognitive complaints, Clinical Dementia Rating scores between 0.5 and 2.0, and at least one cognitive test ≤ 1.5 SD below norms. We defined AT (N) with plasma...
Aging, dementia, and care models: Global perspectives with insights from India
Dementia is an escalating global public health challenge, with India poised to experience one of the largest absolute increases in cases due to rapid demographic aging, lifestyle transitions, and health system constraints. This review critically examines the epidemiology, barriers to diagnosis and care, economic and social impacts, and proposes an integrated dementia care framework for India. While dementia has traditionally been viewed through a social and clinical lens, emerging evidence...
Age-related attenuation of the fast visuomotor network during rapid goal-directed reaching
Humans can react remarkably quickly to novel or displaced visual stimuli when time is of the essence. Such movements are thought to be initiated by a subcortical fast visuomotor network, but it is unclear how this network declines with age. Past work in the upper limb has detailed delayed reaching corrections to jumped visual stimuli in aging, but the underlying mechanisms contributing to these changes of the fast visuomotor network are poorly understood. Conversely, work in the lower limb has...
Age-period-cohort analysis of multimorbidity prevalence among Chinese older adults: from 2002 to 2022
This study aimed to estimate the age, period, and cohort trends of multimorbidity among Chinese older adults from 2002 to 2022, and to explore how these three trends were affected by gender and whether or not living alone. Data were extracted from the China Longitudinal Healthy Living Survey (CLHLS) (2002-2022), and a total of 52,876 valid samples aged 65 to 105 were included. We measured 15 types of chronic diseases, and participants having two or more chronic diseases were considered to have...
Chromogranin A promotes the pathological conversion of alpha-synuclein at the synapse in Parkinson's disease
α-Synuclein (αSyn) aggregation is a prominent hallmark of Parkinson's disease (PD), yet the initial cellular mechanisms are not well understood. In this study, we show that a single day of αSyn preformed fibril (PFF) administration leads to prominent localization of phosphorylated αSyn (p-αSyn) within the pre-synapse of primary neurons. Overexpressing chromogranin A (CgA), which is found in large dense-core vesicles (LDCVs), enhances αSyn aggregation in various neuronal and PD mouse models....
Control of aging-associated neurodegeneration via hypothalamic extracellular vesicles containing parathymosin
Aging-associated neurodegeneration underlies various neurological diseases; however, the neurocrine basis remains poorly understood. Here, we investigate the role of parathymosin (PTMS), a secretory protein with nuclear functions that has recently been identified as a circulating factor in the brain. The results show that loss of PTMS is sufficient to cause severe, age-dependent neurodegeneration and reduced lifespan, whereas hypothalamic PTMS gain of function counteracts aging-associated brain...