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Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer's disease

1 day 2 hours ago
Blood exosomes are emerging as potential biomarkers for diagnosing brain diseases such as Alzheimer's disease (AD). There is currently a lack of an ultrasensitive technology for identifying core AD biomarkers in blood exosomes to optimize the utility of biomarkers in clinical practice. Here, an immunomagnetic exosomal polymerase chain reaction (iMEP) platform was developed using DNA-conjugated antibodies for the rapid detection of amyloid-β (Aβ(1-40) and Aβ(1-42)) and phosphorylated tau...
Shun Hu

The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1

1 day 2 hours ago
Apoptosis signal-regulating kinase 1 (ASK1) is a crucial stress sensor, directing cells toward apoptosis, differentiation, and senescence via the p38 and JNK signaling pathways. ASK1 dysregulation has been associated with cancer and inflammatory, cardiovascular, and neurodegenerative diseases, among others. However, our limited knowledge of the underlying structural mechanism of ASK1 regulation hampers our ability to target this member of the MAP3K protein family towards developing therapeutic...
Karolina Honzejkova

Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling

1 day 2 hours ago
Ultrastructure of human brain tissue has traditionally been examined using electron microscopy (EM) following fixation, staining, and sectioning, which limit resolution and introduce artifacts. Alternatively, cryo-electron tomography (cryo-ET) allows higher resolution imaging of unfixed cellular samples while preserving architecture, but it requires samples to be vitreous and thin enough for transmission EM. Due to these requirements, cryo-ET has yet to be employed to investigate unfixed, never...
Benjamin C Creekmore

Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology

1 day 2 hours ago
A key hallmark of Parkinson's disease (PD) is Lewy pathology. Composed of α-synuclein, Lewy pathology is found both in dopaminergic neurons that modulate motor function, and cortical regions that control cognitive function. Recent work has established the molecular identity of dopaminergic neurons susceptible to death, but little is known about cortical neurons susceptible to Lewy pathology or molecular changes induced by aggregates. In the current study, we use spatial transcriptomics to...
Thomas M Goralski