TABLE 1.
Properties of the proteolytic fragments generated from APP
| APP fragment | Function/Characteristics |
|---|---|
| sAPPβ | Induces neural differentiation of stem cells (65) |
| 100-fold less effective than sAPPα at protecting mouse hippocampal neurons from excitotoxic stress (66) | |
| Cleaved to produce an N-terminal fragment that induced axonal pruning (33) but may be independent of β-secretase activity (32) | |
| CTFβ | Evidence for early pathological accumulation in AD mouse models (67) |
| Disruption of LTP (68) | |
| Linked to learning and memory deficits in AD mouse models (69) | |
| Reduction of spine density and induction of synaptotoxicity (70) | |
| Aβ | The major APP metabolic fragment involved in the initiation and propagation of AD; for recent reviews, see Refs. 1 and 5 |
| sAPPα | Induction of Akt cell survival pathway (71) |
| Protection against neuronal damage caused by traumatic brain injury (72) | |
| Protection against synaptic dysfunction (73) and roles in synaptic plasticity (74) | |
| CTFα | Reduction of spine density and induction of synaptotoxicity (70) |
| Possible role as a γ-secretase inhibitor (75) | |
| p3 | Accumulates in amyloid plaques (76) but less aggregation prone than Aβ (77) |
| Forms calcium permeable ion channels resulting in neuronal toxicity (78) | |
| AICD | Transcriptional regulator regulating several proteins linked to AD (8, 79) |
| Contradictory evidence for a pathological role for AICD in AD (80, 81) | |
| sAPPη/sAPP95 | No specific function described but identified in APP transgenic mouse brain lysates with some discrepancy in molecular weight (22, 23) |
| Aη-α | Inhibited LTP in hippocampal brain slices from mice and suppressed activity in hippocampal neurons (23) |
| Aη-β | Has none of the effects reported for Aη-α (23) |
| CTFη | Indirect evidence that CTFη is a better substrate for BACE1 and γ-secretase cleavage (22) |
| Accumulated in dystrophic neurites surrounding amyloid plaques in transgenic mouse and human AD patient brains (23) | |
| CTFδ | The shorter of the two CTFδ forms accumulated in brain lysates from AD patients (20) |
| sAPPδ (1–448, 1–660, 449–660) | sAPP1–448 neurotoxic to neurons |
| No neurotoxicity was observed for other soluble fragments (20) | |
| N-APP fragments | Increased production of 11-kDa fragment during neuronal differentiation (31) |
| N-APP fragment 18–286 bound neurons with higher affinity than sAPPα via an undetermined receptor and increased phosphatidylinositol phosphate lipid levels (82) |