A1 Adenosine Receptors Accumulate in Neurodegenerative Structures in Alzheimer's Disease and Mediate Both Amyloid Precursor Protein Processing and Tau Phosphorylation and Translocation

In human neuroblastoma SH-SY5Y cells, activating adenosine A1 receptors leads to increased production of soluble amyloid precursor protein fragments through a biochemical pathway involving protein kinase C.

In human nerve cancer cells, activating adenosine A1 receptors causes tau protein to change its chemical state and move within the cell structure via the ERK1/2 signaling pathway.

In Alzheimer's disease, adenosine A2A receptors, normally found in specific brain neurons, are detected in glial cells in the hippocampus and cerebral cortex, showing a change in their location compared to healthy brains.

In people with Alzheimer's disease, the levels of metabotropic glutamate receptors in the hippocampus and cerebral cortex are not different from those in people without the disease, suggesting that changes in receptor expression are specific to adenosine receptors and not a widespread feature of all similar receptors in the brain.

In the brains of people with Alzheimer's disease, adenosine A1 receptors are found in greater amounts inside abnormal protein structures called neurofibrillary tangles and dystrophic neurites, which are located in the hippocampus and cerebral cortex.

Caffeine blocks adenosine receptors in the brain and reduces amyloid plaque accumulation.