ArticleActa neuropathologica2024
SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.
Article in Acta neuropathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed.
- Semaphorin 3G (SEMA3G) is a highly selective marker of cerebral amyloid angiopathy.bioRxiv : the preprint server for biology · 2026Article
- DeepPlaque: a scalable multimodal platform for Aβ pathology and cell analysis in Alzheimer's disease.EMBO molecular medicine · 2026Article
- Proteomic comparison of human neural cell-derived extracellular vesicles and parental cells from Alzheimer's disease and cognitively normal individuals.Science China. Life sciences · 2026Article
- Proteomics of post mortem brains in early- and late-onset Alzheimer's disease: Unraveling differential Aβ effects and potential AD biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Patient cerebral organoids capture Alzheimer's disease proteomic biomarkers and drug targets.bioRxiv : the preprint server for biology · 2026Article
- In vivo profiling of astrocyte secretome reveals brain-region specific regulatory networks in a mouse model of amyloid pathology.Molecular neurodegeneration · 2026Article
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- Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.Biomarker research · 2026Article
- Proteomic signatures of the APOE ε4 and APOE ε2 genetic variants and Alzheimer's disease.Nature aging · 2026Article
- Reproducibility-driven discovery and systematic benchmarking reveal a robust cerebrospinal fluid proteomic signature in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.Research square · 2026Article
- Assessing Aβ-independent effects of Module 42 on immune function in vitro.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Differences in regional developmental origins of glioblastomas revealed by integrated molecular profiling.Journal of neuro-oncology · 2026Article
- Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Brain Region-Specific Accumulation of Amyloidosis-Associated Proteins in Postmortem Brain Tissues of Alzheimer's Disease Patients.Molecular neurobiology · 2025Article
- Cortical Gray Matter Proteins Associated With Cerebral Amyloid Angiopathy in Community-Dwelling Older Adults: An Autopsy Study.Neurology · 2025Article
- Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer's Disease.Biomolecules · 2025Review
- Shared and disease-specific pathways in frontotemporal dementia and Alzheimer's and Parkinson's diseases.Nature medicine · 2025Article
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Abstract
SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain. Therefore, the aim of this study was to examine the distribution of SMOC1 in human AD brain tissue and to determine if SMOC1 influenced amyloid beta (Aβ) aggregation. The distribution of SMOC1 in human brain tissue was assessed in 3 brain regions (temporal cortex, hippocampus, and frontal cortex) using immunohistochemistry in a cohort of 73 cases encompassing advanced AD, mild cognitive impairment (MCI), preclinical AD, and cognitively normal controls. The Aβ- and phosphorylated tau-interaction with SMOC1 was assessed in control, MCI, and advanced AD human brain tissue using co-immunoprecipitation, and the influence of SMOC1 on Aβ aggregation kinetics was assessed using Thioflavin-T assays and electron microscopy. SMOC1 strongly colocalized with a subpopulation of amyloid plaques in AD (43.8 ± 2.4%), MCI (32.8 ± 5.4%), and preclinical AD (28.3 ± 6.4%). SMOC1 levels in the brain strongly correlated with plaque load, irrespective of disease stage. SMOC1 also colocalized with a subpopulation of phosphorylated tau aggregates in AD (9.6 ± 2.6%). Co-immunoprecipitation studies showed that SMOC1 strongly interacted with Aβ in human MCI and AD brain tissue and with phosphorylated tau in human AD brain tissue. Thioflavin-T aggregation assays showed that SMOC1 significantly delayed Aβ aggregation in a dose-dependent manner, and electron microscopy confirmed that the Aβ fibrils generated in the presence of SMOC1 had an altered morphology. Overall, our results emphasize the importance of SMOC1 in the onset and progression of AD and suggest that SMOC1 may influence pathology development in AD.
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