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Quantitative MRI of the hippocampus reveals microstructural trajectories of aging and Alzheimer's disease pathology

1 month 2 weeks ago
Hippocampal degeneration is a feature of both normal aging and Alzheimer's disease (AD). Prior to macroscopic degeneration, microstructural changes occur such as demyelination, iron deposition, or subtle atrophy, which can be characterized in vivo using MRI. We topographically mapped measures of microstructure and macrostructure across the unfolded surface of the hippocampus in 224 healthy older adults at risk for AD (aged 57 to 87) and 37 younger adults (aged 18 to 37). We describe three...
Alfie Wearn

Decreased hippocampal neurite density in late-middle-aged adults following prenatal exposure to higher levels of maternal inflammation

1 month 2 weeks ago
In animal models, exposure to heightened maternal inflammation in utero is associated with altered offspring hippocampal development, including reduced dendritic arborization and density. However, the effects of prenatal maternal inflammation (PNMI) on offspring hippocampal microstructure in humans remain unclear. Here, we examined the relationship between exposure to PNMI and neurite density in the hippocampus and its subfields among offspring during late middle age. Participants included 72...
Raana A Mohyee

Characterization of endothelin-converting enzyme 1 as a key enzyme in the multienzyme Aβ degradation pathway

1 month 2 weeks ago
Altered β-amyloid (Aβ) homeostasis is a critical event triggering the shift from healthy aging to Alzheimer disease (AD) through the overproduction and impaired clearance of Aβ peptides. The Aβ-degrading enzymes (ADEs) are a collective group of proteases that normally promote clearance to counteract Aβ-induced neurodegeneration. We previously discovered that the beta-site amyloid precursor protein cleaving enzyme 1 is an atypical ADE that produces the nontoxic fragment Aβ34 by recognizing 40- or...
Irem Ulku

Impairment of human spatial orientation in the horizontal, but not the vertical plane, due to aging, cognitive decline, or chronic peripheral vestibular loss

1 month 2 weeks ago
INTRODUCTION: Humans and other vertebrates exhibit anisotropic orientation and navigation skills, with better performances in the horizontal compared to the vertical plane. While horizontal navigation accuracy decreases with higher age, less is known about age effects on vertical spatial abilities. The same is true for disorders which cause spatial memory deficits, e.g., cognitive impairment or chronic peripheral vestibular loss.
Johannes Gerb

Asrij/OCIAD1 contributes to age-associated microglial activation and neuroinflammation in mice

1 month 2 weeks ago
Aging is characterized by chronic low-grade neuroinflammation, which increases the risk of neurodegenerative disorders. Neuroinflammation, driven by the activation of astrocytes and microglia, underlies age-associated cognitive deficits. Amplified neuroinflammatory responses to immune challenges are attributed to microglial activation in the aged brain. Despite extensive clinical and experimental evidence linking neuroinflammation to aging, the molecular players that control age-associated...
Prathamesh Dongre

Tortuous extracranial arteries contribute to white Matter hyperintensities in aging brains

1 month 2 weeks ago
INTRODUCTION: White matter hyperintensity (WMH) is a hallmark imaging biomarker of cerebral small vessel disease and are strongly associated with vascular cognitive impairment in the elderly. Morphological changes in large extracranial brain-feeding arteries, such as the internal carotid (ICA) and vertebral arteries (VA), may alter intracranial hemodynamics and contribute to WMH development. This study examined the relationship between arterial tortuosity and WMHs using magnetic resonance...
Zhe Sun

Irradiation-induced brain senescence accelerates cardiac aging via systemic mechanisms: insights from transcriptomic profiling

1 month 2 weeks ago
Aging is characterized by a coordinated functional decline across multiple organs. While cell-autonomous mechanisms contribute to local aging phenotypes, the systemic synchronicity of aging suggests a major role for cell non-autonomous drivers. Emerging evidence implicates the hypothalamus-a central regulator of neuroendocrine and homeostatic functions-as a potential source of circulating pro-geronic signals. A hallmark of brain aging is the accumulation of senescent cells, particularly in...
Rafal Gulej

Sex differences in sleep fragmentation in 5xFAD mice

1 month 2 weeks ago
Sleep alterations have long been associated with Alzheimer's disease (AD), but whether it is an early symptom or only develops later in the pathological progression remains unknown. To study this, 5xFAD heterozygous (Het) mice, a transgenic model of amyloid overexpression, and wild-type (WT) littermates at 1, 2, 3, 4 and 6 months of age were assessed within instrumented home cages to noninvasively score 3-state sleep using respirations and gross body movements during the dark cycle. Progressive...
Kaitlyn J Kim