[Alzheimer's disease. Molecular pathology, animal models, and current treatment].
The currently approved but only mildly efficient drugs against Alzheimer's disease treat merely the symptoms. Genetic, neuropathological, and biochemical data support the importance of the amyloid hypothesis of Alzheimer's disease, at the moment the most influential hypothesis. Many treatment strategies have been performed based on this hypothesis and were markedly successful in preclinical animal models. Unfortunately the treatment is still unsuccessful in humans. This could be due to the animal models showing marginal behavioural deficits but no Alzheimer-like nerve cell loss, although they all developed a more or less pronounced plaque load. Today we know however that Alzheimer plaques are not mainly responsible for the cell loss. Therefore novel animal models have been developed that show age-dependent axonal degeneration, massive neuronal loss, and robust behavioural deficits. Successful treatment of an animal model with such robust deficits would be very likely better suited to transferral into the clinic. The final validation or disproof of individual Alzheimer hypotheses and their resulting treatment strategies can however be obtained only after clinical proof.
Bayer
T A
TA
Klinik für Psychiatrie, Universitätsmedizin Göttingen, Von-Siebold-Strasse 5, 37075, Göttingen. tbayer@gwdg.de
Wirths
O
O
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D018697:Nootropic Agents / Q000627:therapeutic use; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D012183:Retrograde Degeneration / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases