Figure 10

Schematic representation of the somatic and neuritic type of Aβ-related neurodegeneration in frontocentral neurons of APP23 and APP48 mice. In APP48 mice Aβ accumulates within neurons and in microglial cells as previously reported [16]. Extracellular Aβ is not detectable suggesting that APP-independently produced intracellular Aβ leads to functional impairment of neurons as indicated by motor deficits [16]. Mitochondrial alterations occur more frequently in the nerve cell somata of APP48 mice than in wild type and APP23 mice and are proposed to lead to apoptotic cell death as suggested previously [14] without preceding neuritic alteration. This type of somatic neurodegeneration in APP48 mice is different from that seen in APP23 mice, which contain less intracellular Aβ but significant amounts of extracellular Aβ aggregates including plaques. We propose that extra- and intracellular APP-derived Aβ causes synapse loss, dendrite degeneration and often plaque-associated, dystrophic neurites in APP23 mice indicative for a second neuritic type of neurodegeneration. Intracellular Aβ in APP23 mice may be produced within the nerve cell or may be taken up from the extracellular space [13, 57–59].