ArticleBrain pathology (Zurich, Switzerland)2020
Synaptic actin stabilization protein loss in Down syndrome and Alzheimer disease.
Article in Brain pathology (Zurich, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Alzheimer's disease may develop from changes in the immune system, cell cycle, and protein processing following alterations in ribosome function.Scientific reports · 2025Article
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease.Molecular psychiatry · 2024Article
- Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer's disease.Acta neuropathologica · 2024Article
- The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- DNA Hyperstructure.ACS omega · 2024Article
- Measurement of synaptic density in Down syndrome using PET imaging: a pilot study.Scientific reports · 2024Article
- Article
- Enhanced microglial dynamics and paucity of tau seeding in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer's disease.bioRxiv : the preprint server for biology · 2023Article
- The Evaluation of Rac1 Signaling as a Potential Therapeutic Target of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Article
- Cancer and Alzheimer's Inverse Correlation: an Immunogenetic Analysis.Molecular neurobiology · 2023Review
- Article
- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders.Protein & cell · 2022Review
- Review
- Fe65: A Scaffolding Protein of Actin Regulators.Cells · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Reduced spine densities and age-dependent accumulation of amyloid β and tau pathology are shared features of Down syndrome (DS) and Alzheimer's disease (AD). Both spine morphology and the synaptic plasticity that supports learning depend upon the actin cytoskeleton, suggesting that disturbances in actin regulatory signaling might underlie spine defects in both disorders. The present study evaluated the synaptic levels of two proteins that promote filamentous actin stabilization, the Rho GTPase effector p21-activated kinase 3 (PAK3) and Arp2, in DS vs. AD. Fluorescent deconvolution tomography was used to determine postsynaptic PAK3 and Arp2 levels for large numbers of excitatory synapses in the parietal cortex of individuals with DS plus AD pathology (DS + AD) or AD alone relative to age-matched controls. Though numbers of excitatory synapses were not different between groups, synaptic PAK3 levels were greatly reduced in DS + AD and AD individuals vs. controls. Synaptic Arp2 levels also were reduced in both disorders, but to a greater degree in AD. Western blotting detected reduced Arp2 levels in the AD group, but there was no correlation with phosphorylated tau levels suggesting that the Arp2 loss does not contribute to mechanisms that drive tau pathology progression. Overall, the results demonstrate marked synaptic disturbances in two actin regulatory proteins in adult DS and AD brains, with greater effects in individuals with AD alone. As both PAK and the Arp2/3 complex play roles in the actin stabilization that supports synaptic plasticity, reductions in these proteins at synapses may be early events in spine dysfunction that contribute to cognitive impairment in these disorders.
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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.