Open AccessA 1 Adenosine Receptors Accumulate in Neurodegenerative Structures in Alzheimer's Disease and Mediate Both Amyloid Precursor Protein Processing and Tau Phosphorylation and Translocation
Author(s) -
Angulo Ester,
Casadó Vicent,
Mallol Josefa,
Canela Enric I.,
Viñals Francesc,
Ferrer Isidre,
Lluis Carmen,
Franco Rafael
Publication year - 2003
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2003.tb00475.x
Subject(s) - adenosine a1 receptor , receptor , adenosine receptor , adenosine , senile plaques , phosphorylation , alzheimer's disease , biology , medicine , amyloid precursor protein , metabotropic receptor , endocrinology , microbiology and biotechnology , glutamate receptor , agonist , biochemistry , disease
Immunostaining of adenosine receptors in the hippocampus and cerebral cortex from necropsies of Alzheimer's disease (AD) patients shows that there is a change in the pattern of expression and a redistribution of receptors in these brain areas when compared with samples from controls. Adenosine A 1 receptor (A 1 R) immunoreactivity was found in degenerating neurons with neurofibrillary tangles and in dystrophic neurites of senile plaques. A high degree of colocalization for A 1 R and pA4 amyloid in senile plaques and for A 1 R and tau in neurons with tau deposition, but without tangles, was seen. Additionally, adenosine A 2A receptors, located mainly in striatal neurons in controls, appeared in glial cells in the hippocampus and cerebral cortex of patients. On comparing similar samples from controls and patients, no significant change was evident for metabotropic glutamate receptors. In the human neuroblastoma SH‐SY5Y cell line, agonists for A 1 R led to a dose‐dependent increase in the production of soluble forms of amyloid precursor protein in a process mediated by PKC. A 1 R agonist induced p21 Ras activation and ERK1/2 phosphorylation. Furthermore, activation of A 1 R led to and ERK‐dependent increase of tau phosphorylation and translocation towards the cytoskeleton. These results indicate that adenosine receptors are potential targets for AD.