β-APP cognitive function versus β-amyloid-induced cell death

Abstract

The β-amyloid precursor protein (β-APP) has been hypothesized to play an important role in the establishment of synaptic connections. Icv injections of anti-βAPP 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-β-APP- but not control-IgG-injected animals. This suggests a possible involvement of β-APPs in cognitive functions. In order to evaluate the properties of the proteolytic Aβ-fragment accumulating in Alzheimer's disease brains, four different neuronal cell types were exposed to Aβ1-42 for 24 hours. All cells degenerated in response to Aβ, yet chromosomal condensation and internucleosomal DNA fragmentation, typical for apoptosis, occurred in only three of the cell types tested. These findings suggest that β-APPs may play an important role in cognitive processes and additionally, that their alternative proteolytic product Aβ may be differentially toxic to neuronal cell types, inducing cell death either by necrosis or by apoptosis.