ArticleBiological psychiatry2022
Genetic Evidence Supporting a Causal Role of Depression in Alzheimer's Disease.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Evaluating the Bidirectional Causal Effects of Alzheimer's Disease Across Multiple Conditions: A Systematic Review and Meta-Analysis of Mendelian Randomization Studies.International journal of molecular sciences · 2025Pooled it
- mTORC1 Activation Links Chronic Stress to Meso-Circuit Desynchronization and Accelerated Amyloid Pathology via Autophagic Dysfunction.CNS neuroscience & therapeutics · 2026Article
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- Amygdalar Pattern Similarity to Negative and Neutral Images, Ratings of the Images, and PET-Measured Amyloid and Tau Levels in Older Adults Without Dementia.Affective science · 2026Article
- Genetic evidence for a causal role of depression in late-onset Alzheimer disease: A Mendelian randomization study.Medicine · 2026Article
- Multidimensional determinants of depression and non-depression in older adults: evidence from national data.BMC geriatrics · 2026Article
- Large-scale proteomic analyses before depression diagnosis reveal novel pathophysiological insights.Molecular psychiatry · 2026Article
- CSF proteome-wide study of neuropsychiatric symptoms of dementia.medRxiv : the preprint server for health sciences · 2026Article
- Genetic investigation of non-affective psychosis and depression as causal risk factors for dementia.BMJ mental health · 2026Article
- Social network structure and depression by gender in rural Honduras: a cross-sectional study.BMJ open · 2026Observational
- The emergence of neuropsychiatric symptoms in preclinical Alzheimer's disease: An emotion regulation perspective.Neuron · 2026Review
- Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses.BMC medical genomics · 2026Article
- Genetic and Proteomic Investigation of the Smoking-Parkinson's Disease Association.medRxiv : the preprint server for health sciences · 2026Article
- Sleep and stress as modifiable drivers of Alzheimer's disease.NPJ dementia · 2026Review
- Longitudinal analysis of electronic health records reveals medical conditions associated with subsequent Alzheimer's disease development.Alzheimer's research & therapy · 2025Article
- Characterizing Dementia Phenotypes from Unstructured EHR Notes with Generative AI and Interpretable Machine Learning.medRxiv : the preprint server for health sciences · 2025Article
- Disease clusters and their genetic determinants following a diagnosis of depression: analyses based on a novel three-dimensional disease network approach.Molecular psychiatry · 2025Article
- The Emerging Role of the DDAH Proteins in Psychiatric Disorders.Biological psychiatry global open science · 2025Review
- Proteogenomic signature of Alzheimer's disease and related dementia risk in individuals with major depressive disorder.Nature. Mental health · 2025Article
- Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders.BMC medicine · 2025Article
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15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundDepression has been associated with a higher risk of Alzheimer's disease (AD) in several prospective studies; however, mechanisms underlying this association remain unclear.
methodsWe examined genetic correlation between depression and AD using linkage disequilibrium score regression. We then tested for evidence of causality between depression and AD using Mendelian randomization and genome-wide association study results. Subsequently, cis and trans quantitative trait locus analyses for the depression genome-wide association study signals were performed to resolve the genetic signals to specific DNA methylation sites, brain transcripts, and proteins. These transcripts and proteins were then examined for associations with AD and its endophenotypes. Finally, the associations between depression polygenic risk score and AD endophenotypes were examined.
resultsWe detected a significant genetic correlation between depression and AD, suggesting that they have a shared genetic basis. Furthermore, we found that depression had a causal role in AD through Mendelian randomization but did not find evidence for a causal role of AD on depression. Moreover, we identified 75 brain transcripts and 28 brain proteins regulated by the depression genome-wide association study signals through quantitative trait locus analyses. Of these, 46 transcripts and seven proteins were associated with rates of cognitive decline over time, AD pathologies, and AD diagnosis in two separate cohorts, thus implicating them in AD. In addition, we found that a higher depression polygenic risk score was associated with a faster decline of episodic memory over time.
conclusionsDepression appears to have a causal role in AD, and this causal relationship is likely driven, in part, by the 53 brain transcripts and proteins identified in this study.
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