Tomoregulin-2 is found extensively in plaques in Alzheimer's disease brain

Tomoregulin (TR)2 is a transmembrane protein predominantly expressed in brain. It has a unique extracellular domain, containing epidermal growth factor-like and follistatin-like modules. The ectodomain is released from the cell surface, and thought to function as a neurotrophic factor and dendritogenic agent. During CNS development and in the neuronal storage disease GM2 gangliosidosis, which is characterized by ectopic dendrites, the TR2 ectodomain is present in neuronal nuclei where it may function in dendrite initiation. Data presented here demonstrate that TR2 is found extensively in Alzheimer's disease (AD) plaques. Confocal microscopy shows that TR2 is present throughout plaques. Interestingly, TR2 is absent from plaques in the presenilin-1/amyloid precursor protein mouse model of AD. From these data, and what is known about TR2, it is hypothesized that TR2 may participate in amyloid plaque formation and contribute to the pathogenesis of AD. The human TR2 gene is located on chromosome 2q32.3, near a locus linked to Parkinson's disease. TR2 is reported to be a trophic factor for dopaminergic mesencephalic neurons.