Dipeptidyl Peptidase 10 (DPP10(789)): A Voltage Gated Potassium Channel Associated Protein Is Abnormally Expressed in Alzheimer's and Other Neurodegenerative Diseases

The neuropathological features associated with Alzheimer's disease (AD) include the presence of extracellular amyloid-β peptide-containing plaques and intracellular tau positive neurofibrillary tangles and the loss of synapses and neurons in defined regions of the brain. Dipeptidyl peptidase 10 (DPP10) is a protein that facilitates Kv4 channel surface expression and neuronal excitability. This study aims to explore DPP10(789) protein distribution in human brains and its contribution to the neurofibrillary pathology of AD and other tauopathies. Immunohistochemical analysis revealed predominant neuronal staining of DPP10(789) in control brains, and the CA1 region of the hippocampus contained strong reactivity in the distal dendrites of the pyramidal cells. In AD brains, robust DPP10(789) reactivity was detected in neurofibrillary tangles and plaque-associated dystrophic neurites, most of which colocalized with the doubly phosphorylated Ser-202/Thr-205 tau epitope. DPP10(789) positive neurofibrillary tangles and plaque-associated dystrophic neurites also appeared in other neurodegenerative diseases such as frontotemporal lobar degeneration, diffuse Lewy body disease, and progressive supranuclear palsy. Occasional DPP10(789) positive neurofibrillary tangles and neurites were seen in some aged control brains. Western blot analysis showed both full length and truncated DPP10(789) fragments with the later increasing significantly in AD brains compared to control brains. Our results suggest that DPP10(789) is involved in the pathology of AD and other neurodegenerative diseases.