ArticleAnnals of neurology2020
Dysregulation of the Retromer Complex System in Down Syndrome.
Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- EhVps29 Has a Role in the Location of the Retromer Complex and the Function of Key Virulence Factors inMicroorganisms · 2026Article
- Probe-dependent Proximity Profiling (ProPPr) Uncovers Similarities and Differences in Phospho-Tau-Associated Proteomes Between Tauopathies.Molecular neurodegeneration · 2025Article
- VPS35-Retromer: Multifunctional Roles in Various Biological Processes - A Focus on Neurodegenerative Diseases and Cancer.Journal of inflammation research · 2025Review
- VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.Expert opinion on therapeutic targets · 2024Review
- The Role of Oxidative Stress in Trisomy 21 Phenotype.Cellular and molecular neurobiology · 2023Review
- Cathepsin B abundance, activity and microglial localisation in Alzheimer's disease-Down syndrome and early onset Alzheimer's disease; the role of elevated cystatin B.Acta neuropathologica communications · 2023Article
- Association of Retromer Deficiency and Tau Pathology in Down Syndrome.Annals of neurology · 2022Article
- Review
- Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- An Outlook on the Complexity of Protein Morphogenesis in Health and Disease.Frontiers in molecular biosciences · 2022Review
- Down syndrome and type I interferon: not so simple.Current opinion in immunology · 2021Review
- Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology.Annals of neurology · 2021Review
- Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21).Scientific reports · 2021Article
- Mechanistic Analysis of Age-Related Clinical Manifestations in Down Syndrome.Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMost of the patients with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by age 40. Although this increased susceptibility to AD in DS is thought to be primarily due to triplication of the amyloid precursor protein located on chromosome 21, the precise molecular mechanisms are not well understood. Recent evidence has implicated defective protein sorting and trafficking secondary to deficiencies in retromer complex proteins in AD pathogenesis. Thus, the objective of the present study is to assess the retromer complex system in DS.
methodsHuman postmortem brain tissue and fibroblasts from subjects with DS and healthy controls were examined for the various retromer protein components using Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR).
resultsRetromer recognition core proteins were significantly decreased in DS fibroblasts, and in both the hippocampi and cortices of young (age 15-40 years old) and aged (40-65 years old) subjects with DS compared with controls. Correlation analyses showed a significant inverse relationship between recognition core proteins and levels of soluble forms of Aβ 1-40 and 1-42 in both hippocampus (n = 33, Spearman = -0.59 to -0.38, p ≤ 0.03 for VPS35, VPS26, VPS29, and VPS26B) and cortex tissue (n = 57, Spearman = -0.46 to -0.27, p ≤ 0.04 for VPS35, VPS26, and VPS29) of the same patients.
interpretationWe conclude that dysregulation of the retromer complex system is an early event in the development of the AD-like pathology and cognitive decline in DS, and for this reason the system could represent a novel potential therapeutic target for DS. ANN NEUROL 2020 ANN NEUROL 2020;88:137-147.
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