Review Article
Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity
Table 1
Summary of known synaptic effects of altering BACE1.
| | Age | Aβ | Basal synaptic transmission | Presynaptic function | LTP | LTD | Reference |
| | BACE1 KO | 3–6 mo | No A or A | Normal (CA1 and CA3) | Increased PPF ratio (CA1 and CA3) | Normal LTP (4x TBS) but larger dedepression in CA1; no mossy fiber LTP (3x 100 Hz) and no dedepression in CA3 | Normal LTD (paired-pulse 1 Hz) in CA1, but slightly larger LTD (paired-pulse 1 Hz) in CA3 | [164, 174] |
| | BACE1 KO + activation of 7-nAChRs | 3–6 mo | No A or A | Normal (CA3) | Restored PPF ratio (CA3) | Rescued mossy fiber LTP (CA3) (3x 100 Hz) | | [175] |
| |
BACE1+/−; 5XFAD APP/PS1 (Tg6799) | 6 mo | 66% decrease in A and 57% in A in brain; reduce amyloid plaque burden in hippocampus by 78% and anterior cingulate cortex by 44% | Remained significantly reduced (CA1) | | Restored LTP to WT control levels (CA1) (3x TBS) | | [176] |
| | Adenoviral-Fbx2* in Tg2576 | 12–14 mo | 30% decrease in A | No change | | Improved the impaired LTP (CA1) (3x TBS) 4 weeks after adenoviral injection | | [177] |
|
|
*Transfected into hippocampus. Fbx2 facilitates BACE1 degradation.
|
