Table 2.
RyR expression 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] |
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.