Receptor-effector coupling dysfunctions in Alzheimer's disease.

There is now good evidence that in the AD brain, a number of neurotransmitter effector systems are defective. Such abnormalities include defective G, protein and protein kinase C function as well as a drastically reduced level of receptors for the second messenger Ins(1,4,5) P3. Such changes are probably not restricted to the late stages of the disease, and are found in regions of the brain that show little histopathological abnormality, such as the cerebellum. Whether these changes precede or are secondary to primary histopathological changes such as beta-amyloid deposition is not as yet clear. What is clear, however, is that such signal transduction abnormalities are likely to negate therapeutic benefits in clinical strategies based upon the tenet of neurotransmitter replacement.