TABLE 2.

AD-related behavioral deficits, histopathology and loss of neuronal viability in 5xFAD and EFAD mice

Model		Phenotype
		<4 Months	4–8 Months	8–12 Months	12–16 Months	≥16 Months
5xFAD	Behavioral deficits
	Learning, exploration and memory	↑	↑↑	↑↑↑	↑↑↑↑	↑↑↑↑
		(MWM)	(YM, MWM, FC, NOR)	(YM, MWM, FC, CTA)	(YM, MWM, FC, CM)	(YM)
	Histopathology
	Aβ deposition	↑↑	↑↑↑	↑↑↑↑	↑↑↑↑↑	↑↑↑↑↑↑
	Plaque deposition	↑↑	↑↑↑	↑↑↑↑	↑↑↑↑	n.m.
			(♀ > ♂)	(♀ > ♂)	(♀ > ♂)
	CAA	↑	↑↑	↑↑↑	n.m.	n.m.
	Neuroinflammation	↑	↑↑	↑↑↑	↑↑↑↑	↑↑↑↑
	pTau	↑	↑	↑↑	—	n.m.
	Neuronal viability
	Synaptic protein loss	↑	↑↑	↑↑↑	↑↑↑	n.m.
	Neuroplasticity	↑	↑↑	↑↑↑	n.m.	n.m.
	Neuronal loss	—	↑*	↑↑*	↑↑↑	n.m.
EFAD	Behavioral deficits
	Learning, exploration and memory	—	↑	↑	n.m.	n.m.
			(MWM: ♀ε4 > ε3 ≥ ε2, YM: ♀ε4 > ε3 ≥ ε2)	(YM: ε4 > ε3; ε4 ♀ > ♂, NOR: ε4 ♀ > ♂; ♀ ε4 > ε3)
	Histopathology
	Aβ deposition	—	↑	↑↑	n.m.	n.m.
			(ε4 > ε3 ≥ ε2; ♀ > ♂)	(ε4 > ε3; ♀ > ♂)
	Plaque deposition	—	↑	n.m.	n.m.	n.m.
			(ε4 > ε3 ≥ ε2; ♀ > ♂)
	CAA	n.m.	↑	n.m.	n.m.	n.m.
			(ε4 > ε3; ♀ = ♂)
	Neuroinflammation	n.m.	↑	n.m.	n.m.	n.m.
			(ε4 > ε3)
	pTau	—	↑	n.m.	n.m.	n.m.
			(ε4 > ε3)
	Neuronal viability
	Synaptic protein loss	—	↑	n.m.	n.m.	n.m.
			(♀ε4 > ε3 ≥ ε2; ♂ε4 > ε3)
	Neuroplasticity	n.m.	n.m.	n.m.	n.m.	n.m.
	Neuronal loss	n.m.	n.m.	n.m.	n.m.	n.m.

5xFAD mice: Behavioral deficits: MWM (49, 50, 59–61, 340), YM (49, 51, 54, 55, 58), fear conditioning (FC) (52, 56, 57), NOR (329, 330), conditioned taste aversion (CTA) (52), cross-maze (CM) (62). AD-related histopathology: Aβ deposition: immunohistochemistry (IHC)-mAb to Aβ (50, 52, 55, 58, 62–65, 68, 329–337); plaque deposition: Thio-S (50, 64, 69, 332, 334); CAA: Thio-S, methoxy-X04 (334, 341); neuroinflammation: astrogliosis or microgliosis: IHC-mAb to GFAP or ionized calcium binding adaptor molecule 1 (Iba1)/F4-80 (50, 55, 58, 61, 65, 329, 333–335); pTau: Western blot for p-sites (59, 342). Neuronal viability: Synaptic proteins: PSD95, synaptophysin, syntaxin by Western blot or IHC (50, 68, 69); neuroplasticity: basal synaptic transmission, long-term potentiation or paired-pulse facilitation (56, 57, 61, 329–331, 335, 336, 343–345); neuronal loss: cresyl violet, IHC-mAb to RNA binding protein, fox-1 homolog 3 (NeuN): *quantified by area (50, 185), or using unbiased stereology (61–63, 68, 69, 334, 338, 346). EFAD mice: Behavioral deficits: MWM, YM, NOR (70, 71). AD-related histopathology: Aβ deposition: IHC-mAb to Aβ42-specific (MOAB-2) (66, 71) or IHC-mAb to Aβ (4G8) (73); plaque deposition: Thio-S (66, 71, 257); CAA: Thio-S (73); neuroinflammation: IHC-mAb to GFAP or Iba1 (72); pTau: Western blot for p-sites (75). Neuronal viability: synaptic proteins: PSD95, synaptophysin, drebrin by Western blot (70, 172). The levels are represented as low ↑ to high ↑↑↑↑↑↑ relative to an earlier age or, if known and significant, differences between sex or APOE genotypes are specifically indicated within each cell relative to an earlier age. n.m., not measured; —, not detectable.