beta-APP cognitive function versus beta-amyloid--induced cell death.
The beta-amyloid precursor protein (beta-APP) has been hypothesized to play an important role in the establishment of synaptic connections. Icv injections of anti-beta APP antibodies into rat brains produced no appreciable effect on subsequent learning of a passive avoidance task whereas memory assessed 1 day later in a retention test was impaired in anti-beta-APP--but not control-IgG-injected animals. This suggests a possible involvement of beta-APPs in cognitive functions. In order to evaluate the properties of the proteolytic A beta-fragment accumulating in Alzheimer's disease brains, four different neuronal cell types were exposed to A beta 1-42 for 24 hours. All cells degenerated in response to A beta, yet chromosomal condensation and internucleosomal DNA fragmentation, typical for apoptosis, occurred in only three of the cell types tested. These findings suggest that beta-APPs may play an important role in cognitive processes and additionally, that their alternative proteolytic product A beta may be differentially toxic to neuronal cell types, inducing cell death either by necrosis or by apoptosis.
Gschwind
M
M
Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Martin
J R
JR
Moreau
J L
JL
Huber
G
G
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D016923:Cell Death; D003071:Cognition / Q000502:physiology*; D006224:Cricetinae; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009498:Neurotoxins; D010446:Peptide Fragments