Although age has been recognized as a risk factor for late-onset dementia of Alzheimer type, its etiology is unknown as yet. Several age-related metabolic abnormalities may thus become important for the pathogenesis of the late-onset form. Studies at the cellular/molecular level in brain tissue are possible post mortem, but lack information on the beginning of the disorder. In this supplement, different approaches are dealt with how to induce structural and/or metabolic abnormalities in relevant cell cultures, in brain slices and in experimental animals, and how behavioral changes parallel the metabolic variations.

InhaltsangabePrimary cultures of neurons for testing neuroprotective drug effects.- Regulation of proteolytic processing of the amyloid ?-protein precursor in Alzheimer's disease in transfected cell lines and in brain slices.- Glutamate, beta-amyloid precursor proteins, and calcium mediated neurofibrillary degeneration.- An aggregate brain cell culture model for studying neuronal degeneration and regeneration.- The organotypic entorhinal-hippocampal complex slice culture of adolescent rats. A model to study transcellular changes in a circuit particularly vulnerable in neurodegenerative disorders.- The use of ion-sensitive electrodes and fluorescence imaging in hippocampal slices for studying pathological changes of intracellular Ca2+ regulation.- The cultured fibroblast model.- Psychometric testing in rats during normal ageing. Procedures and results.- Ultrastructural changes in brain parenchyma during normal aging and in animal models of aging.- Morphological hippocampal changes during normal aging and their relation to cognitive deterioration.- The function of the NMDA-receptor during normal brain aging.- Age-related alterations by chronic intermittent hypoxia on cerebral synaptosomal ATPase activities.- Impairment in memory function and neurodegenerative changes in the cholinergic basal forebrain system induced by chronic intake of ethanol.- Dysfunction of the brain cholinergic system during aging and after lesions of the nucleus basalis of Meynert.- Receptor function in cortical rat brain regions after lesion of nucleus basalis.- Trophic factors during normal brain aging and after functional damage.- Alzheimer's disease and transgenic mice.- An aspect of Alzheimer neuropathology after suicide transport damage.- AF64A-induced brain damage and its relation to dementia.- Desensitization of brain insulin receptor. Effect on glucose/energy and related metabolism.