ReviewAging cell2007
Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store.
Review in Aging cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
200 citing papers in PubMed, 2 syntheses or guidelines pooled it, 380 citations in OpenAlex.
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- Pooled it
- The effect of dietary approaches to stop hypertension (DASH) diet on attention-deficit hyperactivity disorder (ADHD) symptoms: a randomized controlled clinical trial.European journal of nutrition · 2021Trial
- Presenilin-1 controls glycolysis and identity of pancreatic beta cells.Communications biology · 2026Article
- Role of tRNA-Derived Fragments and Their Modifications in the Pathogenesis and Treatment of Alzheimer's Disease.Molecular neurobiology · 2025Review
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- GRPa-PRS: A risk stratification method to identify genetically-regulated pathways in polygenic diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet-Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Longevity mechanisms in cardiac aging: exploring calcium dysregulation and senescence.Biogerontology · 2025Review
- Characterizing positive and negative quantitative susceptibility values in the cortex following mild traumatic brain injury: a depth- and curvature-based study.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- The senescent synapse: A look at autophagy, calcium handling, and mitochondrial bioenergetics at the synapse in ageing and Parkinson's disease.Current research in physiology · 2025Review
- Article
- Bats as instructive animal models for studying longevity and aging.Annals of the New York Academy of Sciences · 2024Review
- Calcium channel signalling at neuronal endoplasmic reticulum-plasma membrane junctions.Biochemical Society transactions · 2024Review
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Hippocampal hyperphosphorylated tau-induced deficiency is rescued by L-type calcium channel blockade.Brain communications · 2024Article
- Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease.Physiological reviews · 2024Review
- A biophysical minimal model to investigate age-related changes in CA1 pyramidal cell electrical activity.PloS one · 2024Article
- Defective cerebellar ryanodine receptor type 1 and endoplasmic reticulum calcium 'leak' in tremor pathophysiology.Acta neuropathologica · 2023Article
- Retrosplenial cortex microglia and perineuronal net densities are associated with memory impairment in aged rhesus macaques.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. In addition, other studies have reported aging- or AD model-related alterations in Ca2+ release from ryanodine receptors (RyR) on intracellular stores. The Ca2+-sensitive RyR channels amplify plasmalemmal Ca2+ influx by the mechanism of Ca2+-induced Ca2+ release (CICR). Considerable evidence indicates that a preferred functional link is present between L-VGCCs and RyRs which operate in series in heart and some brain cells. Here, we review studies implicating RyRs in altered Ca+ regulation in cell toxicity, aging, and AD. A recent study from our laboratory showed that increased CICR plays a necessary role in the emergence of Ca2+-related biomarkers of aging. Consequently, we propose an expanded L-VGCC/Ca2+ hypothesis, in which aging/pathological changes occur in both L-type Ca2+ channels and RyRs, and interact to abnormally amplify Ca2+ transients. In turn, the increased transients result in dysregulation of multiple Ca2+-dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.