[Neuropathology of Alzheimer's disease and mild cognitive impairment].
The neuropathological hallmarks of Alzheimer s disease (AD) are the presence of senile (neuritic) plaques (NP), neurofibrillary tangles (NFT), synapse loss, and neuronal cell loss. Large neurons are more affected than small ones. AD patients can also have other non specific lesions, such as granulovacuolar degeneration, Hirano bodies, and Lewy bodies. AD patients present a loss of many cholinergic neurons, especially those located in the nucleus basalis of Meynert, as well as a decrease of choline acetyl transferase (ChAT) activity, which suggested that the core of the cognitive deficits of AD was caused by the loss of cholinergic input. Interestingly, recent studies conducted in subjects with mild cognitive impairment (MCI) (these are patients that are at risk of developing AD) have shown that these subjects can have NP and NFT in the neocortex and allocortex, with relatively normal levels of ChAT in a variety of brain regions. This suggests the structures of the cholinergic system are preserved in early stages of the disease. Scientists have made significant advances in understanding both the clinical manifestations and pathobiological manifestations of AD. However, the mechanisms of specific vulnerability of the cholinergic system to AD, as well as the initial process that leads to the complex neuropathological lesions are unknown.
López
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Departamento de Neurología, Facultad de Medicina, Universidad de Pittsburgh, Pittsburgh, PA 15213, USA. lopezol@msx.upmc.edu
DeKosky
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D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology*; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000172:deficiency; D003072:Cognition Disorders / Q000473:pathology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000032:analysis; D018377:Neurotransmitter Agents / Q000502:physiology
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D002795:Choline O-Acetyltransferase