Scott A. Small

Disrupting SORL1-retromer endosomal recycling in mice drives the age-dependent neurodegenerative signature of Alzheimer's disease

This study shows that disrupting SORL1-retromer recycling in mice leads to age-dependent brain atrophy resembling Alzheimer's disease, which can be reversed by restoring SORL1 function.

RhoGEF12 regulates endosomal SORL1-retromer and its inhibition is therapeutic in human neuronal models of Alzheimer's disease

Pharmacological inhibition of RhoGEF12 increases endosomal SORL1-retromer recycling and reduces pathogenic amyloid secretion in human neuronal models, identifying a novel, targetable pathway for treating Alzheimer's disease.

In vivo evidence that SORL1, encoding the endosomal recycling receptor SORLA, can function as a causal gene in Alzheimer's Disease

This study shows that SORL1 haploinsufficiency in pigs mimics early AD biomarker changes without neurodegeneration, supporting its role as a causal gene in Alzheimer's disease.

Retromer Combinatorials for Gene-Therapy Across a Spectrum of Neurological Diseases

The paper tests combinatorial gene therapy for retromer-related neurological diseases by expressing VPS35 with VPS26 paralogs in neurons, showing synergistic effects on retromer function and Sorl1 levels.

Retromer repletion with AAV9-VPS35 restores endosomal function in the mouse hippocampus

This study shows that restoring VPS35 in the hippocampus of mice with chronic neuronal VPS35 depletion rescues APP cleavage and glutamate receptor levels, and reduces glial activation similar to Alzheimer's disease.