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Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes. Proactive treatment options remain limited, largely due to a lack of sensitive and convenient diagnostics, especially early in disease progression or specifically for small fiber neuropathy (SFN), the dying back of distal small diameter nerves. Here, we report on the design, testing, and validation of a novel medical diagnostic device for the functional assessment of small fiber nerves: an electrically conductive needle array designed to record nerve activity signals in the skin and transdermal tissues, which we call the DEN (Detecting Early Neuropathy). DEN recordings were validated across a time course of high fat diet-induced DPN in mice. Based on preclinical mouse data, the device was then adapted to obtain recordings in human tissue. DEN recordings successfully recorded various types of neural activity. New functional diagnostic tools like DEN offer a promising outlook for patients needing an earlier and more sensitive diagnosis of SFN/DPN, which will allow for earlier and more effective treatment options such as implementation of glucose regulation strategies.

Alzheimer’s disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There is significant variation in age at onset and severity of symptoms highlighting the importance of genetic diversity in the study of AD. To address this, we analyzed cell and pathology composition of 6- and 14-month-old AD-BXD mouse brains using the semi-automated workflow (QUINT); which we expanded to allow for nonlinear refinement of brain atlas-registration, and quality control assessment of atlas-registration and brain section integrity. Near global age-related increases in microglia, astrocyte, and amyloid-beta accumulation were measured, while regional variation in neuron load existed among strains. Furthermore, hippocampal immunohistochemistry analyses were combined with bulk RNA- sequencing results to demonstrate the relationship between cell composition and gene expression. Overall, the additional functionality of the QUINT workflow delivers a highly effective method for registering and quantifying cell and pathology changes in diverse disease models.