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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.