CCR1 Is an Early and Specific Marker of Alzheimer's Disease

Chemokines are a diverse group of small proteins that effect cell signaling by binding to G-protein-coupled, seven-transmembrane receptors. Our group had found previously that the chemokine receptor CCR1 was present in neurons and dystrophic processes in a small sample of Alzheimer's disease cases. This expanded immunohistochemical study shows that the number of CCR1-positive plaque-like structures in the hippocampus and entorhinal cortex is highly correlated to dementia state as measured by the clinical dementia rating score. CCR1 immunoreactivity is found in dystrophic, neurofilament-positive, synaptophysin-negative neurites that are associated with senile plaques containing amyloid beta peptides of the 1-42 species (Aβ42). CCR1 was not, however, associated with diffuse deposits of Aβ42. There was limited expression of CCR1 in neurofibrillary tangle-bearing neuritic processes. Astrocytes and microglia were typically negative for CCR1. Human brains from age-matched, nondemented individuals rarely displayed either CCR1 or Aβ42 immunoreactivity. Seven other types of dementing neurodegenerative diseases were examined, and all failed to demonstrate CCR1 immunopositivity unless Aβ42-positive plaques were also present. Thus, neuronal CCR1 is not a generalized marker of neurodegeneration. Rather, it appears to be part of the neuroimmune response to Aβ42-positive neuritic plaques.