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Table 2 RyR expression in Alzheimer disease

From: Ryanodine receptors: physiological function and deregulation in Alzheimer disease

AD samples/models Brain regions/study systems AD stage (*) RyR expression (**) References
Human AD post-mortem brains Hippocampal regions (Subiculum, CA1, CA2) Early stages (I-II) ↑ [3H] RyR binding [107]
Human AD post-mortem brains Hippocampal regions (Subiculum, CA1, CA2, CA3, and CA4) Late stages (V-VI) ↔ [3H] RyR binding [107]
↓RyR2 mRNA
PS1 L285V, PS1M146V mutations PC12 cells   ↑ RyR3 mRNA and protein [95]
PS1M146V KI Tg mice Primary neurons
Human AD post-mortem brains mid frontal cortex   ↓RyR2-3 mRNA splice variants [108]
MCI post-mortem brains mid temporal and mid frontal cortex   ↑RyR2 mRNA; ↔ RyR3 mRNA [108]
mid frontal cortex ↓RyR2 mRNA splice variant;
mid temporal cortex ↑RyR2 mRNA splice variant
Extracellular Aβ42 application Primary cortical neurons   ↑RyR3 mRNA; [91]
↔ RyR1-2 mRNA
CRDN8 Tg mice Primary cortical neurons 4-4.5 (mo) ↑RyR3 mRNA [91]
Whole brains ↑RyR3 protein
3xTgAD mice Primary hippocampal neurons   ↑RyR protein [78]
PS1M146V KI Tg mice 3xTgAD mice Whole brains 6 (w) ↑RyR protein [72, 110]
6 (mo) ↔ RyR protein
1.5 (Y) ↑RyR protein
3xTgAD mice Hippocampus 6-8 (w) ↑RyR2 mRNA; [94, 100]
↔ RyR1-3 mRNA
Tg2576 mice Cortex 15-18 (mo) ↑RyR2 mRNA; [92]
↔ RyR1-3 mRNA
↑RyR proteins
APPWt and APPswe mutation SH-SY5Y cells   ↑RyR1-2-3 mRNA [92]
↑RyR proteins
PScDKO Tg mice Hippocampus 2 (mo) ↓ RyR proteins [97]
↓ [3H] RyR binding
↔ RyR mRNA
Subletal Aβ oligomers Primary hippocampal neurons   ↓ RyR 2–3 mRNA [105]
↓ RyR 2 protein
APPswePS1L166P Tg mice Hippocampus 3 and 6 (mo) ↑RyR 2–3 protein [111]
  1. Abbreviations: (*) AD stage is defined following BRAAk’s staging for human AD post-mortem brains, and is referred in weeks (W), months (mo) or years (Y) in AD mice models, (**) RyR expression (mRNA or protein level) is depicted as ↑ (increased), ↓ (reduced), or ↔ (unchanged) as compared to respective controls, PS presenilin, MCI mild cognitive impairment, KI knock in, Tg transgenic, Wt wild type, CRDN8 Tg mice express human APP with a double mutation (APPK670N/M671L + APPV717F), PScKO Tg mice are conditionally double knock out for PS1 and PS2, Tg2576 mice express the Swedish double mutation (APP695K670N/M671L), 3xTgAD mice are generated from the PS1M146VKI mouse overexpressing APPswe and TauP130L.