Diagnostic and inclusion criteria in Alzheimer's disease clinical trials: A systematic review of the past decade.

Background: Dementia, mainly caused by Alzheimer's disease (AD), is a leading cause of mortality and disability in the elderly. However, inconsistencies in diagnostic and inclusion criteria challenge the design and comparability of AD clinical trials.

Objective: To review recent AD clinical trials, focusing on diagnostic methods and inclusion criteria, and identify trends and gaps to inform future research.

3D printing of structural bionic and functionalized hydrogels for the construction of macroscale human cardiac tissues.

Capturing the intricate structural, mechanical, and electrophysiological properties of the native heart in models is crucial for achieving efficient physiological pumping function; however, current approaches have shown limited success in replicating these features essential for producing tissue models on complex geometries that accurately mimic full cardiac function. Here, we present a novel hydrogel ink formulation combining a conductive, biocompatible ionic liquid with a photosensitive poly(vinyl alcohol)-based hydrogel, enabling 3D printing of biomechanically compatible heart valves and 3D tissue engineering scaffolds. These scaffolds mimic the helical and circumferential alignments characteristic of the ventricular and atrial muscle layers, respectively, and incorporate a hollow auxetic structure to achieve mechanical anisotropy.

SLC39A13 Regulates Heart Function via Mitochondrial Iron Homeostasis Maintenance.

Background: Iron is a necessary trace element for multiple reactions but is toxic in excess. Its intracellular balance is delicately maintained. We previously found that the loss of SLC39A13 (solute carrier family 39 member 13)/ZIP13 (zinc-iron permease 13), a newly identified endoplasmic reticulum/Golgi-resident iron transporter, impacted iron homeostasis in multiple tissues.

The regulation of rhythmic locomotion by motor cortical and dopaminergic inputs in the mouse striatum.

The striatum is a critical component of the basal ganglia and plays a central role in regulating motor initiation and action selection. How cortical and subcortical inputs converging at the striatum regulate locomotion remains unclear. By examining gait changes in head-fixed mice running on a treadmill, we found that mice were capable of performing forward, but not backward, rhythmic locomotion using their forelimbs when the striatum and motor cortex were inactivated.

Spotlight on Alzheimer's disease and related dementias research in East Asia.

With a burgeoning dementia burden driven by unique demographic, genetic, and socioeconomic factors of East Asia, the region has made significant investments in understanding disease mechanisms, developing biomarkers, and exploring therapeutic approaches. This collection highlights the current landscape of Alzheimer's disease and related dementias research in East Asia, including region-specific epidemiological insights, advances in plasma biomarkers and neuroimaging, and innovative diagnostic and treatment strategies. Despite progress, challenges such as limited access to advanced imaging, cultural barriers to autopsy, and disparities in healthcare persist.

Higher Educational Attainment and Accelerated Tau Accumulation in Alzheimer Disease.

Importance: The impact of educational attainment (EA) on longitudinal tau accumulation remains largely underexplored.

Objective: To investigate the association of EA with tau accumulation in Alzheimer disease (AD).

Design, Setting, And Participants: This cohort study used 3 independent samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; October 2015-July 2022, mean follow-up: 3.

Protocol for high-efficiency generation of iPSCs stably expressing Cas9-EGFP using the selection by essential gene exon knockin method.

CRISPR-Cas9 is widely used for genome editing. However, Cas9 silencing occurs during the directed differentiation of induced pluripotent stem cells (iPSCs), even when it is inserted into the safe harbor locus. Here, we generate iPSC-Cas9-EGFP using selection by essential gene exon knockin technology.

Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice.

Introduction: Presenilin (PS) gene mutations cause memory impairment in early-onset familial Alzheimer's disease (FAD), but the underlying mechanisms remain unclear.

Methods: We examined the effects of the PS1 M146V FAD mutation on motor learning, motor learning-related changes in neuronal Caactivity and CREB phosphorylation in the primary motor cortex.

Results: We found that PS1 M146V knock-in mice displayed long-term deficiencies in motor skill learning.

Mitochondrial protein nmd regulates lipophagy and general autophagy during development.

Lipophagy engulfs lipid droplets and delivers them to lysosomes for degradation. We found that lipophagy levels were low in most fly tissues, except for the prothoracic gland (PG) during larval development. Therefore, we performed a small-scale screening in the PG to identify regulators of lipophagy.

Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population.

Over 20% of patients with Alzheimer's disease (AD) worldwide are Chinese, although the efficacy of existing blood-based measures of AD biomarkers is largely unknown in Asian cohorts. Here we explored how plasma tau biomarkers correlated with cross-sectional and longitudinal AD-related outcomes and their diagnostic performance in 1,085 participants from three independent studies, including two Chinese cohorts, Greater-Bay-Area Healthy Aging Brain Study (n = 425) and Huashan (n = 297), and the North American Alzheimer's Disease Neuroimaging Initiative cohort (n = 363). Plasma p-tau217 performed best in classifying Aβ-positron emission tomography (PET) and tau-PET positivity throughout the AD continuum and correlated with all AD-related outcomes.

SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.

The COVID-19 pandemic is caused by the enveloped virus SARS-CoV-2. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation.

Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline.

Introduction: Baseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood.

Methods: We investigated dynamic changes of CSF GAP-43 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years.

Results: Individuals with hippocampal atrophy, AD-signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid/tau status.

White matter fractional anisotropy decreases precede hyperintensities in Alzheimer's disease.

The associations of β-amyloid (Aβ) and tau deposition with white matter (WM) degeneration in Alzheimer's disease (AD) remain inadequately elucidated. We investigate baseline and longitudinal changes of microstructural fractional anisotropy (FA) and macrostructural white matter hyperintensities (WMHs) and their relationships with Aβ and tau positron emission tomography (PET) and vascular risk factors in different Aβ/tau stages defined by PET imaging. Lower levels and faster decline rates of FA occur in the AD continuum, particularly in tau-positive individuals.

Atypical Cadherin FAT2 Is Required for Synaptic Integrity and Motor Behaviors.

In humans, mutations or deletions of atypical FAT cadherin genes are linked to autism spectrum disorder and cerebellar ataxia. However, their large genomic size and the enormous size of their encoded proteins have hampered functional studies, leaving the roles of FAT cadherins poorly understood. To address this gap, we investigated FAT2-an atypical cadherin selectively expressed in cerebellar granule cells-in murine cerebellar function.

Interpretable MRI-Based Deep Learning for Alzheimer's Risk and Progression.

Timely intervention for Alzheimer's disease (AD) requires early detection. The development of immunotherapies targeting amyloid-beta and tau underscores the need for accessible, time-efficient biomarkers for early diagnosis. Here, we directly applied our previously developed MRI-based deep learning model for AD to the large Chinese SILCODE cohort (722 participants, 1,105 brain MRI scans).

Spatial-temporal interactions between white matter hyperintensities and multiple pathologies across the Alzheimer's disease continuum.

Introduction: The interactive relationships between Alzheimer's disease (AD) and white matter hyperintensities (WMHs) in multiscale brain structural networks still need to be clarified.

Methods: Based on subjects enrolled from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, regional WMHs, amyloid beta (Aβ) accumulation, and microstructural changes detected by diffusion weighted imaging (DWI) in multiscale brain networks were modeled by time-evolving graphs; their interactive relationships were further investigated using Granger causality after constructing pseudo-time subject sequences.

Results: In up to 86% of the extracted pseudo-time subject sequences, Aβ was determined to be the Granger cause of WMHs in the structural connectivity of the inferior longitudinal fasciculus (ILF).

Distinct oxytocin signaling pathways synergistically mediate rescue-like behavior in mice.

Spontaneous rescue behavior enhances the well-being and survival of social animals, yet the neural mechanisms underlying the recognition and response to conspecifics in need remain unclear. Here, we report that observer mice experience distress when encountering anesthetized conspecifics, prompting spontaneous rescue-like behavior toward the unconscious mice. This behavior facilitates the earlier awakening of anesthetized mice while simultaneously alleviating stress in the helper mice.

Generation of stable Cas9-EGFP expressing human induced pluripotent stem cell lines based on SeLection by Essential-gene Exon Knock-in technology.

Here, we used SeLection by Essential-gene Exon Knock-in technology to generate the iPSC line with constitutive expression of Cas9-EGFP, while retaining all functions of the essential gene. Cas9-EGFP was inserted into the GAPDH exon9 via the homologous recombination, avoiding Cas9 silencing that often occurs during iPSC differentiation. The edited cell line shows precise knock-in locus with the typical characteristics and pluripotency of iPSCs.

Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution.

Microglia, essential in the central nervous system (CNS), were historically considered absent from the peripheral nervous system (PNS). Here, we show a PNS-resident macrophage population that shares transcriptomic and epigenetic profiles as well as an ontogenetic trajectory with CNS microglia. This population (termed PNS microglia-like cells) enwraps the neuronal soma inside the satellite glial cell envelope, preferentially associates with larger neurons during PNS development, and is required for neuronal functions by regulating soma enlargement and axon growth.

Higher plasma soluble TREM2 correlates with reduced cerebral tau accumulation in Alzheimer's disease.

Loss-of-function mutation of triggering receptor expressed on myeloid cell 2 (TREM2) is associated with increased risks for Alzheimer's disease (AD). Recent animal studies reveal that the activation of peripheral TREM2 signaling may affect cerebral β-amyloid (Aβ) and tau aggregates. However, the underlying relationship between peripheral TREM2 and brain AD pathology has not yet been well-elucidated in the aging population.

Ectopic protein lysine methacrylation contributes to defects caused by loss of HIBCH or ECHS1.

The absence of HIBCH or ECHS1, two Leigh syndrome genes, in cultured cells results in abnormal mitochondrial morphology and respiratory defects. Fly eyes lacking either protein exhibit age-dependent degeneration. Elevated lysine methacrylation (Kmea) is observed in both HIBCH- and ECHS1-deficient cells and fly tissues.

The Dose-Dependent Effects of Fluorocitrate on the Metabolism and Activity of Astrocytes and Neurons.

Background: Fluorocitrate (FC) ranging from 5 μM to 5 mM is often used as a specific metabolic inhibitor of the astrocytes to study astrocytic functions. Whether FC at such concentrations may affect neuronal metabolism and function remains unclear.

Methods: We examined the effects of FC on the ATP levels and Ca activity of the astrocytes and neurons in the motor cortices of living mice using two-photon microscopy.

Transcription and epigenetic factor dynamics in neuronal activity-dependent gene regulation.

Neuronal activity, including sensory-evoked and spontaneous firing, regulates the expression of a subset of genes known as activity-dependent genes. A key issue in this process is the activation and accumulation of transcription factors (TFs), which bind to cis-elements at specific enhancers and promoters, ultimately driving RNA synthesis through transcription machinery. Epigenetic factors such as histone modifiers also play a crucial role in facilitating the specific binding of TFs.