ArticleScience translational medicine2023
Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 4 of them syntheses that pooled it.
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Who cites it
94 citing papers in PubMed, 4 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- A systematic review and meta-analysis of metalloproteinases in patients with Alzheimer's disease and mild cognitive impairment.Journal of Alzheimer's disease : JAD · 2026Pooled it
- Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Peripheral immune function and Alzheimer's disease: a living systematic review and critical appraisal.Molecular psychiatry · 2024Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease.Journal of neuroinflammation · 2025Trial
- Biomarkers of cellular senescence predict risk of mild cognitive impairment: Results from the lifestyle interventions for elders (LIFE) study.The journal of nutrition, health & aging · 2025Trial
- Longitudinal Dynamics of the Blood Proteome Within the Alzheimer Spectrum in Down Syndrome.Neurology · 2026Article
- Epilepsy as a Disorder of Neuroimmune Metabolism: The Kynurenine Pathway as a Link Between Cognitive and Psychiatric Dysfunction.Biomolecules · 2026Review
- Aptamer-Based Platforms for Human Aging Biomarkers: Multiplexed Proteomics, Biosensors and Translational Perspectives.International journal of molecular sciences · 2026Review
- Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.Brain : a journal of neurology · 2026Article
- ProLM: a plasma proteomics pretrained model for the general population.Nature communications · 2026Article
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- Multiorgan transcriptomics and circulating extracellular vesicle profiling reveal age-dependent systemic vulnerability to isoflurane anesthesia and surgery.GeroScience · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.Research square · 2026Article
- Proteomic signature of dementia risk in type 2 diabetes.Journal of advanced research · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026Article
- CMV titer associations with cognition and the plasma proteome implicate FLT1 and neurovascular mechanisms as potential moderators.Journal of neuroinflammation · 2026Article
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Novel Plasma Proteomic Markers and Risk of Venous Thromboembolism.Circulation · 2026Article
- A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation.Nature immunology · 2026Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 11 institutions in 3 countries.
Funding
Abstract
A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that 12 of these 32 dementia-associated proteins were associated with cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, or neuroinflammation. We found that eight of these candidate protein markers were abnormally expressed in human postmortem brain tissue from patients with AD, although some of the proteins that were most strongly associated with dementia risk, such as GDF15, were not detected in these brain tissue samples. Using network analyses, we found a protein signature for dementia risk that was characterized by dysregulation of specific immune and proteostasis/autophagy pathways in adults in midlife ~20 years before dementia onset, as well as abnormal coagulation and complement signaling ~10 years before dementia onset. Bidirectional two-sample Mendelian randomization genetically validated nine of our candidate proteins as markers of AD in midlife and inferred causality of SERPINA3 in AD pathogenesis. Last, we prioritized a set of candidate markers for AD and dementia risk prediction in midlife.
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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.