The neurobiology and microbiology of Alzheimer’s disease
The neuropathological characteristics of Alzheimer’s disease (AD) are the presence of neurofibrillary tangles, senile neuritic plaques, loss of neurons, and cerebral amyloid angiopathy. However, it seems that the loss of synapsis is the most important structural lesion associated with severity and progression of dementia. The neurodegenerative processes that cause AD are unknown. However, it is accepted that the accumulation of stable ßamyloid proteins is the central pathogenic event. All mutations known to cause AD are related to increase production of ßamyloid proteins. Deposits of neurotoxic forms of amyloid (a beta-pleated sheet configuration) can cause a destructive event, which can lead to the loss of neurotransmitters that disrupt cell-to-cell communications, abnormal synthesis and accumulation of cytoskeletal proteins (e.g., tau), loss of synapses, altered oxidative metabolisms, and finally, to neuronal death. There is a selective vulnerability of the limbic system and heteromodal sensory areas to AD pathology, and it is in these areas where amyloid deposits can induce an inflammatory process. The most affected neurotransmitter in AD is acetylcholine, and this is associated with loss of the enzymes that are part of its metabolic pathway, with loss of presynaptic receptors (e.g., M2), and with a relative preservation of postsynaptic receptors (e.g., M1). These advances in the understanding of the neurodegenerative processes that characterize AD are the starting points for future treatments, such as transmitter replacement therapies, antioxidant agents, estrogens, nerve growth factors, and drugs that could interfere with amyloid formation
