CCR1 is an early and specific marker of Alzheimer's disease

• Published in: Annals of neurology 2003-11, Vol.54 (5), p.638-646
• Main Authors: Halks-Miller, Meredith, Schroeder, Miriam L., Haroutunian, Vahram, Moenning, Ursula, Rossi, Michael, Achim, Cristian, Purohit, Dushyant, Mahmoudi, Mithra, Horuk, Richard
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Biological and medical sciences; Biomarkers - analysis; Brain - metabolism; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Humans; Immunohistochemistry; Medical sciences; Microscopy, Confocal; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; Peptide Fragments - metabolism; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Receptors, CCR1; Receptors, Chemokine - metabolism
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.10733

Chemokines are a diverse group of small proteins that effect cell signaling by binding to G‐protein–coupled, seven‐trans‐membrane 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.