Alzheimer's disease and related disorders annual, 2002 by Jeffrey L Cummings, Serge Gauthier

By Jeffrey L Cummings, Serge Gauthier

Given the advance of latest healing innovations and items, Serge Gauthier and Jeffrey Cummings have compiled an inventory of latest themes so as to be of curiosity basically to neurologists concentrating on Alzheimer's illness, and likewise to psychiatrists and geriatricians. The members, all revered of their subspecialties, have written updated, comprehensively referenced chapters which should supply tips in addition to stimulate dialogue on the place present therapy is heading.

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The presence of active caspase fragments, either detected in the cell by immunohistochemistry or in homogenates by cleavage of fluorogenic substrates, has often been accepted as evidence that a cell is undergoing apoptosis and as evidence that the detected caspase is playing a crucial role in the death pathway. However, detection of an activated caspase in postmortem tissue or in cellular extracts proves neither that apoptosis is occurring nor that the caspase is involved in neuronal death. 35 In this case, the activation of caspase-3 was initially assayed by cleavage of DEVD-AFC, a fluorogenic substrate, but it was also confirmed by immunohistochemical demonstration of an increase in the active fragment of caspase-3.

The generation of free radicals associated with Aβ deposition and neuronal stress90–96 can also contribute to neuronal loss by rendering the cells vulnerable to the higher levels of IL-1β in the AD brain leading to reduced function and death by protein nitration and the generation of products such as 4-hydroxynonenol which can lead to death directly through a caspase-3dependent mechanism. 97,98 Apoptosis in AD is a complex phenomenon that has different properties depending on when it is observed in the course of the disease and on the genetic constitution of the individual.

103. Henriksson BG, Soderstrom S, Gower AJ et al. Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats. Behav Brain Res 1992; 48:15–20. 104. Holtzman DM, Li Y, Chen K et al. Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration. Neurology 1993; 43:2668–2673. 105. Broe GA, Grayson DA, Creasey HM et al. Anti-inflammatory drugs 37 protect against Alzheimer disease at low doses. Arch Neurol 2000; 57:1586–1591. 106.

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