Neural Plasticity

Review Article

Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity

Table 2

Summary of alterations in synaptic function by altering presenilin or -secretase activity.


	Age	A	Basal synaptic transmission	Presynaptic function	LTP	LTD	Other	Reference

PS1 cKO	3–6 mo	Cortical A and A are decreased	Normal (CA1)	Normal PPF ratio (CA1)	Normal (CA1) (5x TBS) normal (CA1) (3x 100 Hz)	Normal (CA1)		[178]

	2 mo		Normal (CA1)	Decreased PPF ratio (CA1)	Decreased (CA1) (5x TBS)	Normal (CA1)	Reduced NMDAR function (CA1); decreased cortical synaptic levels of NR1, NR2A, αCaMKII, and CRE-dependent genes	[179]
	6 mo		Increased (CA1)	Decreased PPF ratio (CA1)	Decreased (CA1) (5x TBS)	Normal (CA1)
PS cDKO	2 mo						Increased expression of the NR2A subunit of NMDARs, specifically at postsynaptic density and presynaptic terminals of axo/dendritic synapses, trapped at synapses (CA1)	[180]
	5 wk			Decreased Ca²⁺-dependent frequency facilitation and release probability (CA1)	Normal (CA1) (5x TBS)		Normal NMDAR-mediated synaptic response (CA1)	[181]
	6 wk				Decreased (CA1) 5x TBS		Reduced NMDAR-mediated synaptic response (CA1)

CA1-PS cDKO	2 mo			Normal (CA1)	Normal (CA1) (5x TBS)		Normal NMDAR/AMPAR ratio	[182]

CA3-PS cDKO	2 mo			Decreased Ca²⁺-dependent frequency facilitation and release probability (CA1)	Decreased (CA1) (5x TBS)		Normal NMDAR/AMPAR ratio	[182]

AppTg (Swe/Ind)	3 mo		Normal (CA1)	Normal (CA1)	Increased (CA1) (5x TBS)			[183]
	6 mo	Age dependent increase in Aβ levels and plaque deposition	Decreased (CA1)	Normal (CA1)	Decreased (CA1) (5x TBS)

AppTg; PS1^−/−	3 mo		Normal (CA1)	Normal (CA1)	Increased (CA1)			[183]
	6 mo	Decreased cortical Aβ peptides and plaque formation	Decreased (CA1)	Normal (CA1)	Decreased (CA1) (5x TBS)

	3-4 mo		Normal (CA1)		Normal (CA1)
Tg2576	6-7 mo	50% increase in soluble Aβ	Decreased (CA1)-stronger stimulus required to elicit similar sized postsynaptic responses		Decreased (CA1)			[184]
	14-15 mo	1000% increase in soluble A	Decreased (CA1) but similar to 6-7 months		Normal (CA1)

Tg2576 w/MRK-560 (-secretase inhibitor)	6-7 mo	1, 3, or 7 days of treatment reduced soluble A levels	Partial recovery but not significant		Recovered (CA1)			[184]
Tg2576 w/MRK-560 (-secretase inhibitor)	15 mo	3 months of treatment reduced soluble A levels	No improvement

Tg2576 w/CHF5074 (-secretase modulator)	6 mo	4-week, subchronic, oral treatment reduced A levels			Recovered (CA1)			[185]