[Neurobiology and molecular biology of Alzheimer's disease].
BACKGROUND
The neuropathological characteristics of Alzheimer's disease (AD) include the presence of neurofibrillary tangles (NFT), senile plaques (SP), neuronal death, and amyloid angiopathy. However, it is accepted that the accumulation of beta amyloid proteins, which are the main constituent of the SP, is the central neuropathological lesion in AD. All mutations that known to cause AD are related to an increase production of beta amyloid. An inflammatory process usually surrounds the SP, and it is though to contribute to the formation of the SP, and to the metabolic cascade that leads to neuronal death. There is seveltive vulnerability of the limbic system and heteromodal areas to AD pathology, and it is in these areas where amyloid deposits can induce a greater inflammatory response. The most affected neurotransmitter is acetylcholine, and it is associated with the loss of enzymes that are part of ots normal metabolism, and with loss of a presynaptic receptors (e.g. Muscarinic 2), and with a relative preservation of postsynaptic receptors (e.g. Muscarinic1). There is significant loss of nicotinic receptors.


CONCLUSIONS
Significant advances have been made with transgenic mice that enhanced our understanding of AD pathology. It has been identified enzymes that participate in the metabolism of amyloid, and the possible mechanisms of interaction between amyloid deposits and NFT. These advances are the starting point for future treatments that could interfere with amyloid formation
DeKosky
S T
ST
University of Pittsburgh, Pittsburgh, PA 15213, USA.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008125:Locus Coeruleus / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D016874:Neurofibrillary Tangles / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013569:Synapses / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter