Ryanodine receptors: physiological function and deregulation in Alzheimer disease

Topic: Amyloid, tau and blood-test diagnosis

Perturbed Endoplasmic Reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in Alzheimer disease (AD). Accordingly, different studies have reported alterations of the expression and the function of Ryanodine Receptors (RyR) in human AD-affected brains, in cells expressing familial AD-linked mutations on the β amyloid precursor protein (βAPP) and presenilins (the catalytic core in γ-secretase complexes cleaving the βAPP, thereby generating amyloid β (Aβ) peptides), as well as in the brain of various transgenic AD mice models. Data converge to suggest that RyR expression and function alteration are associated to AD pathogenesis through the control of: i) βAPP processing and Aβ peptide production, ii) neuronal death; iii) synaptic function; and iv) memory and learning abilities.

Key findings

• Accordingly, different studies have reported alterations of the expression and the function of Ryanodine Receptors (RyR) in human AD-affected brains, in cells expressing familial AD-linked mutations on the β amyloid precursor protein (βAPP) and presenilins (the catalytic core in γ-secretase complexes cleaving the βAPP, thereby generating amyloid β (Aβ) peptides), as well as in the brain of various transgenic AD mice models.
• Data converge to suggest that RyR expression and function alteration are associated to AD pathogenesis through the control of: i) βAPP processing and Aβ peptide production, ii) neuronal death; iii) synaptic function; and iv) memory and learning abilities.
• In this review, we document the network of evidences suggesting that RyR could play a complex dual "compensatory/protective versus pathogenic" role contributing to the setting of histopathological lesions and synaptic deficits that are associated with the disease stages.
• We also discuss the possible mechanisms underlying RyR expression and function alterations in AD.

Why it matters

This review describes altered expression and function of ryanodine receptors in Alzheimer's-affected brains, in cells with familial mutations, and in transgenic mouse models, linking them to amyloid production, neuronal death, synaptic function and memory. It is a summary of findings across models and reports no treatment, cure or prevention.

New to this subject? Start with our plain-English guide: Genetics →

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1186/1750-1326-9-21
• PubMed: 24902695
• Original source →
• Free full text: Molecular Neurodegeneration →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{delprete2014-24902695,
  author  = {Del Prete, D. and Checler, F. and Chami, M.},
  title   = {{Ryanodine receptors: physiological function and deregulation in Alzheimer disease}},
  journal = {Molecular neurodegeneration},
  year    = {2014},
  doi     = {10.1186/1750-1326-9-21},
  pmid    = {24902695},
  url     = {https://doi.org/10.1186/1750-1326-9-21}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Ryanodine receptor blockade reduces amyloid-β load and memory impairments in Tg2576 mouse model of Alzheimer disease The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012-08-01 · usefulness score 47/100 · Risk genes beyond APOE
• Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1 The Journal of clinical investigation · 2007-04-12 · usefulness score 45/100 · Risk genes beyond APOE

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• Role of Microglia and Astrocytes in Alzheimer's Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation Cells · 2022-09-01 · usefulness score 47/100 · Inflammation and the immune system

Related studies in Risk genes beyond APOE

• S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production Molecular and cellular neurosciences · 2005-01-01 · usefulness score 44/100
• Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors Science (New York, N.Y.) · 1992-10-01 · usefulness score 55/100
• Not just amyloid: physiological functions of the amyloid precursor protein family Nature reviews. Neuroscience · 2017-03-31 · usefulness score 53/100
• Physiological functions of APP family proteins Cold Spring Harbor perspectives in medicine · 2012-02-01 · usefulness score 45/100
• Amyloid precursor protein processing is stimulated by metabotropic glutamate receptors Proceedings of the National Academy of Sciences of the United States of America · 1995-08-01 · usefulness score 45/100
• Nuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations The Journal of biological chemistry · 2012-05-31 · usefulness score 45/100

Similar studies

• Glucose metabolism and insulin receptor signal transduction in Alzheimer disease 2004 · Risk genes beyond APOE
• Deciphering the Role of Adrenergic Receptors in Alzheimer’s Disease: Paving the Way for Innovative Therapies 2025 · Disease mechanisms
• Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease 2012 · Genetics
• Sarcopenia and Muscle Functions at Various Stages of Alzheimer Disease 2018 · Cognitive tests and assessment
• The role of TNF and its receptors in Alzheimer's disease 2001 · Genetics
• Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy 2009 · Genetics

More on Risk genes beyond APOE

• A review that covers this ground Pathological and physiological functions of presenilins Molecular neurodegeneration · 2006-06-12 · usefulness score 44/100
• Newest in this subject Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Temporal Proteomics Links the APP London Mutation to Early Cholesterol Remodeling Cell Programs in Human Neurons bioRxiv · 2026-10-24 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Risk genes beyond APOE →