ArticleMolecular brain2015
Evidence that the presynaptic vesicle protein CSPalpha is a key player in synaptic degeneration and protection in Alzheimer's disease.
Article in Molecular brain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A Meta-Analysis on Presynaptic Changes in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Pooled it
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- Identifying transcriptomic signatures that mediate the causal effect of genotype on Alzheimer's disease.Frontiers in neuroscience · 2026Article
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Investigating the expression profiles of cysteine string proteins (CSPs) in cochlear tissue.Journal of otology · 2024Article
- Decoding transcriptomic signatures of cysteine string protein alpha-mediated synapse maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.EMBO reports · 2023Article
- Review
- CSPα in neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- Disruption of the VAPB-PTPIP51 ER-mitochondria tethering proteins in post-mortem human amyotrophic lateral sclerosis.Frontiers in cell and developmental biology · 2022Article
- Cysteine string protein alpha accumulates with early pre-synaptic dysfunction in Alzheimer's disease.Brain communications · 2022Article
- Emerging insights into synapse dysregulation in Alzheimer's disease.Brain communications · 2022Review
- Discovery of Novel Drug Candidates for Alzheimer's Disease by Molecular Network Modeling.Frontiers in aging neuroscience · 2022Article
- Synaptic tau: A pathological or physiological phenomenon?Acta neuropathologica communications · 2021Review
- Cysteine String Protein Controls Two Routes of Export for Misfolded Huntingtin.Frontiers in neuroscience · 2021Article
- Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer's disease brain.Neurobiology of disease · 2020Article
- Lemur Tyrosine Kinase 2 (LMTK2) Level Inversely Correlates with Phospho-Tau in Neuropathological Stages of Alzheimer's Disease.Brain sciences · 2020Article
- Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease.Scientific reports · 2019Article
- Biological function of Lemur tyrosine kinase 2 (LMTK2): implications in neurodegeneration.Molecular brain · 2018Review
- The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn Alzheimer's disease synapse loss precedes neuronal loss and correlates best with impaired memory formation. However, the mechanisms underlying synaptic degeneration in Alzheimer's disease are not well known. Further, it is unclear why synapses in AD cerebellum are protected from degeneration. Our recent work on the cyclin-dependent kinase 5 activator p25 suggested that expression of the multifunctional presynaptic molecule cysteine string protein alpha (CSPalpha) may be affected in Alzheimer's disease.
resultsUsing western blots and immunohistochemistry, we found that CSPalpha expression is reduced in hippocampus and superior temporal gyrus in Alzheimer's disease. Reduced CSPalpha expression occurred before synaptophysin levels drop, suggesting that it contributes to the initial stages of synaptic degeneration. Surprisingly, we also found that CSPalpha expression is upregulated in cerebellum in Alzheimer's disease. This CSPalpha upregulation reached the same level as in young, healthy cerebellum. We tested the idea whether CSPalpha upregulation might be neuroprotective, using htau mice, a model of tauopathy that expresses the entire wild-type human tau gene in the absence of mouse tau. In htau mice CSPalpha expression was found to be elevated at times when neuronal loss did not occur.
conclusionOur findings provide evidence that the presynaptic vesicle protein CSPalpha is a key player in synaptic degeneration and protection in Alzheimer's disease. In the forebrain CSPalpha expression is reduced early in the disease and this may contribute to the initial stages of synaptic degeneration. In the cerebellum CSPalpha expression is upregulated to young, healthy levels and this may protect cerebellar synapses and neurons to survive. Accordingly, CSPalpha upregulation also occurs in a mouse model of tauopathy only at time when neuronal loss does not take place.
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