Evidence for a novel neuronal mechanism driving Alzheimer's disease, upstream of amyloid.

This perspective offers an alternative to the amyloid hypothesis in the etiology of Alzheimer's disease (AD). We review evidence for a novel signaling mechanism based on a little-known peptide, T14. T14 could drive neurodegeneration as an aberrantly activated process of plasticity selective to interconnecting subcortical nuclei, the isodendritic core, where cell loss starts at the pre-symptomatic stages of the disease.

Development and Validation of a Novel Mobility Test for Rod-Cone Dystrophies: From Reality to Virtual Reality.

Purpose: To validate a novel mobility test (MOST, MObility Standardized Test) and performance outcomes in real (RL) and virtual (VR) environments to be used for interventional clinical studies in order to characterize vision impairment in rod-cone dystrophies, also known as retinitis pigmentosa (RP).

Design: Prospective, interventional, noninvasive, reliability and validity analysis.

Methods: We designed MOST to be used in both VR and RL and conducted 3 experimental studies with 89 participants to (1) validate the difficulty of the mobility courses (15 controls), (2) determine the optimal number of light levels and training trials (14 participants with RP), and (3) validate the reproducibility (test-retest), reliability (VR/RL), sensitivity, and construct/content validity of the test (30 participants with RP and 30 controls).

Characterization of a Bioactive Peptide T14 in the Human and Rodent Substantia Nigra: Implications for Neurodegenerative Disease.

The substantia nigra is generally considered to show significant cell loss not only in Parkinson's but also in Alzheimer's disease, conditions that share several neuropathological traits. An interesting feature of this nucleus is that the pars compacta dopaminergic neurons contain acetylcholinesterase (AChE). Independent of its enzymatic role, this protein is released from pars reticulata dendrites, with effects that have been observed in vitro, ex vivo and in vivo.

A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.

Introduction: The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood.

Methods: Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts-AD and a transgenic mouse model-to investigate T14, a 14mer peptide, as a key signaling molecule in the neuropathology.

Results: T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to that seen in AD: neurons immunoreactive for T14 in proximity to T14-immunoreactive plaques.

Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics.

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements.