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White matter hyperintensities (WMH) are associated with cortical thinning in distant brain regions. However, it is currently unclear how WMH affect neurodegeneration in early Alzheimer's disease (AD). Here, we investigated associations between WMH and cortical thickness in temporal regions involved in early AD (AD cortical signature), while correcting for regional amyloid and tau accumulation assessed by PET. We performed cross-sectional (n = 551), and longitudinal (n = 125) analyses in older...

Alterations in mitochondrial ultrastructure and reduced levels of the crista-shaping protein Opa1 are key features of mitochondrial myopathies and aging. We identify and characterize a biological therapy that improves mitochondrial and disuse myopathy models by boosting Opa1 levels. In silico analysis identifies microRNAs (miRNAs) 128-3p and 148/152-3p family as conserved modulators of OPA1 transcription and elevated in various muscle disorders. These miRNAs target the 3' UTR of murine and human...

Gerascophobia-the excessive fear of aging-is linked to health anxiety and negative body perceptions. While health anxiety may heighten aging-related fears, body image satisfaction may buffer this effect. However, their interplay remains underexplored, particularly among community-dwelling middle-aged and older adults not receiving psychological care. This study aims to examine the predictive role of health anxiety on gerascophobia and assess whether body image satisfaction moderates this...

Education is related to a wide variety of beneficial health, behavioral, and societal outcomes. However, whether education causes long-term structural changes in the brain remains unclear. A pressing challenge is that individuals self-select into continued education, thereby introducing a wide variety of environmental and genetic confounders. Fortunately, natural experiments allow us to isolate the causal impact of increased education from individual (and societal) characteristics. Here, we...

One of the agency’s largest and most storied research facilities will be closed along with most forest research stations

Findings speak to the dramatic impact ants and termites can have on mammalian evolution

Mitophagy is a selective type of autophagy that removes damaged mitochondria to maintain mitochondrial homeostasis and regulate the antiviral immune response. Despite increasing evidence that herpes simplex virus type 1 (HSV-1) infection causes mitochondrial damage, the regulatory mechanisms governing mitochondrial homeostasis and its biological implications in the context of HSV-1 infection and viral encephalitis remain unclear. In our recent work, we find that HSV-1 infection causes the...

Network hyperexcitability is one of the hallmarks of the early stage of Alzheimer's disease (AD). In this issue of Neuron, Papanikolaou¹ and coworkers show that AD-mediated alterations start at the excitatory-inhibitory subcircuit in the deep layers of the cortex.

Despite the increasing availability of biomarkers in clinical settings, diagnosing individuals with subtle cognitive/behavioral symptoms and normal structural brain imaging remains challenging. In real-world settings, it is not feasible to subject all such patients to costly and invasive second-level assessments, and there are no clear guidelines for identifying those who should undergo these procedures beyond clinical follow-up and structural imaging. The present study explores the potential of...

In this issue of Neuron, Graves et al.¹ report that genetically reducing senescent cells by deleting p16 in a tauopathy mouse model significantly lessens tau pathology, neurovascular dysfunction, and behavioral deficits. Their study highlights the crucial role of p16-dependent senescence in microglia and endothelial cells as active drivers of neurodegeneration.

The human cortex exhibits remarkable morphometric similarity between regions; however, the form and extent of lifespan network remodeling remain unknown. Here, we show the spatiotemporal maturation of morphometric brain networks, using multimodal neuroimaging data from 33,937 healthy participants aged 0-80 years. Global architecture matures from birth to early adulthood through enhanced modularity and small worldness. Early development features cytoarchitecturally distinct remodeling: sensory...

Stem cells maintain tissue architecture by replacing differentiated cells at steady state and upon injury. Implementing this cornerstone role requires protection of stem cells from pathogens and from the toxic effects of immune system activation. However, the pro-inflammatory innate immune mechanisms that protect differentiated cells from infection are poorly functional in stem cells. Instead, stem cells employ other specific defence mechanisms, such as antiviral RNA interference. At steady...