Neurotransmitter Receptor—G-Protein-Mediated Signal Transduction in Alzheimer’s Disease

Abstract

Alzheimer’s disease is the most frequent cause of dementia in the elderly and is characterized clinically by a progressive loss of memory, intellect, and personality. The characteristic neuropathological hallmarks of Alzheimer’ s disease are the extracellular deposition of a 39–43 amino acid protein termed β-amyloid (or Aβ), in the cerebrovasculature (1) and cores of senile plaques (2), as well as the formation of paired helical filaments (PHFs) that com­prise intracellular neurofibrillary tangles (NFTs) (3), neuropil threads, and senile plaque neurites. The principal component of PHFs is an abnormally hyperphosphorylated form of the microtubule-associated protein tau (4). Other features of Alzheimer’s disease pathology include neuronal and syn­aptic fallout that disrupts neurotransmission via the ascending cholinergic, noradrenergic, and serotonergic projections to the neocortex, as well as corti­cal excitatory amino acidergic pyramidal neurones.