Yagi et al., 2011 |
fAD: PS1 A246E mutation, PS2 N141I mutation |
Neurons |
Elevated Aβ42/Aβ40. |
Compound E (γ-secretase inhibitor) and compound W (Aβ42 inhibitor) reduced Aβ42 and Aβ40. High dose compound W reduced Aβ42/Aβ40 ratio. |
Israel et al., 2012 |
fAD: duplication of APP sAD |
Neurons |
Aβ(1-40), phospho-tau, aGSK-3β increase, large RAB5-positive early endosomes. |
β-secretase inhibitor reduces phospho-tau and aGSK-3β. |
Koch et al., 2012 |
fAD: PS1 L166P mutation, PS1 D385N mutation |
iPSC and embryonic derived NSCs |
Elevated Aβ42/Aβ40. Decreased Aβ40, while Aβ42 did not differ from control. Partial loss of γ-secretase function. |
γ-secretase inhibitor and non-steroidal anti-inflammatory drugs reduce Aβ. |
Duan et al., 2014 |
sAD: ApoE3/E4 |
Basal forebrain cholinergic neurons |
Elevated Aβ42/Aβ40. Elevated sensitivity to calcium influx and glutamate toxicity. |
Low dose of γ-secretase inhibitor elevates Aβ secretion in sAD, while it typically reduces Aβ in fAD. |
Kondo et al., 2013 |
fAD: APP-E693Δ mutation and APP-V717L mutationsAD |
Neurons |
Intracellular Aβ aggregation in APP-E693Δ line, while no significant extracellular plaque aggregation was observed. Endoplasmic reticulum and oxidative stress response in APP-E693Δ line. |
Docosahexaenoic acid (DHA) reduces stress response in APP-E693Δ and one of two sporadic patients. |
Muratore et al., 2014 |
fAD: APP-V717L mutation |
Neurons |
Elevated Aβ42 and Aβ38. Increased β-secretase cleavage of APP. Altered γ-secretase cleavage site Hyperphosphorylated tau. |
Aβ-specific antibody reduce elevated tau. |
Sproul et al., 2014 |
fAD: PS1 A246E mutation, PS1 M146L mutation |
Neural progenitor cells, neurons |
Elevated Aβ42/Aβ40, more apparent in NPCs than neurons. 14 genes (e.g., NLRP2, ASB9, NDP) are recognized to alter expression in PS1 mutated patients’ NPCs, 5 of them involved in late-onset AD as well. |
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Hossini et al., 2015 |
sAD |
Neurons |
Elevated GSK3β activity and phosphorylated tau. Generate an AD-related protein network. Ubiquitin-proteasome system function is down-regulated in sAD. |
γ-secretase inhibitor down regulates phosphorylated tau. |
Moore et al., 2015 |
fAD: PS1 Y115C mutation, PS1 intron 4 mutation, APP V717I mutation, APP duplication |
Neurons |
All lines demonstrated increased Aβ42 generation. APP mutations show elevated phenotype while PS1 mutations did not. |
γ-secretase inhibitor increased intracellular tau, β-secretase inhibitor reduced intracellular tau. γ-secretase modulation reduced intracellular tau. |
Young et al., 2015 |
sAD: SORL1 SNPs (risk variants and Protective variants) |
Neurons |
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BDNF treatment reduces Aβ by SORL1–dependent upregulation in protective homozygotes or heterozygotes. In risk homozygotes, BDNF treatment is not effective in reducing Aβ. Overexpression of SORL1 cDNA ameliorates Aβ. |
Woodruff et al., 2016 |
fAD: PS1 ΔE9 mutation, APP V717F mutation, APP Swedish mutation |
Neurons |
APP and LDL endocytosis and soma-to-axon transcytosis of lipoproteins dysfunction in fAD. |
β-secretase inhibitor recovers endocytosis function. |
Jones et al., 2017 |
fAD and sAD |
Astrocytes Neural progenitor cells |
Atrophy and abnormal localization of astrocytes from both fAD and sAD, while NPCs did not show evident pathology. |
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