ArticleThe American journal of psychiatry2018
Synaptic Proteome Compensation and Resilience to Psychosis in Alzheimer's Disease.
Article in The American journal of psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer's disease-associated genes: DTNB and DLG2.Molecular psychiatry · 2022Pooled it
- Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.Molecular psychiatry · 2021Pooled it
- A clinical and experimental investigation of liraglutide effects on the brain-kidney axis.Science advances · 2026Article
- Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs.Molecular psychiatry · 2025Article
- The genetic landscape of early-onset Alzheimer's disease in China.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A brain DNA co-methylation network analysis of psychosis in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Beyond memory impairment: the complex phenotypic landscape of Alzheimer's disease.Trends in molecular medicine · 2024Review
- Psychosis in Alzheimer's disease is associated with specific changes in brain MRI volume, cognition and neuropathology.Neurobiology of aging · 2024Article
- Unique transcriptional signatures correlate with behavioral and psychological symptom domains in Alzheimer's disease.Translational psychiatry · 2024Article
- Unveiling the Enigma: Exploring Risk Factors and Mechanisms for Psychotic Symptoms in Alzheimer's Disease through Electronic Medical Records with Deep Learning Models.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeting the post-synaptic proteome has therapeutic potential for psychosis in Alzheimer Disease.Communications biology · 2023Article
- Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder.Schizophrenia bulletin · 2022Article
- Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities.Nature reviews. Neurology · 2022Review
- Psychosis in Alzheimer's Disease Is Associated With Increased Excitatory Neuron Vulnerability and Post-transcriptional Mechanisms Altering Synaptic Protein Levels.Frontiers in neurology · 2022Article
- Psychosis as a Treatment Target in Dementia: A Roadmap for Designing Interventions.Journal of Alzheimer's disease : JAD · 2022Review
- Fingolimod mitigates synaptic deficits and psychosis-like behavior in APP/PSEN1 mice.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Psychosis in Alzheimer's Disease.Current neurology and neuroscience reports · 2020Review
- Hippocampal sclerosis, TDP-43, and the duration of the symptoms of dementia of AD patients.Annals of clinical and translational neurology · 2020Article
- Animal Models of Psychosis in Alzheimer Disease.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2020Review
- Genetic associations with psychosis and affective disturbance in Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe presence of psychosis in Alzheimer's disease denotes a phenotype with more rapid cognitive deterioration than in Alzheimer's disease without psychosis. Discovery of novel pharmacotherapies that engage therapeutic targets for prevention or treatment of Alzheimer's disease with psychosis would benefit from identifying the neurobiology of resilience to psychosis in Alzheimer's disease. The primary objective of this study was to determine whether alterations in the synaptic proteome were associated with resilience to psychotic symptoms in Alzheimer's disease and, if present, were independent of neuropathologic burden.
methodQuantitative immunohistochemistry was used to measure multiple neuropathologies in dorsolateral prefrontal cortex from subjects with early and middle-stage Alzheimer's disease who differed in psychosis status. Synaptic proteins were quantified by liquid chromatography-mass spectrometry in gray matter homogenates from these subjects and from neuropathologically unaffected subjects. The synaptic proteome was similarly evaluated in cortical gray matter homogenate and in postsynaptic density fractions from an APPswe/PSEN1dE9 mouse model of amyloidosis with germline reduction in Kalrn, which has been shown to confer resilience to progression of psychosis-associated behaviors relative to APPswe/PSEN1dE9 alone.
resultsSubjects resilient to psychotic symptoms in Alzheimer's disease had higher levels of synaptic proteins compared with those with psychosis and unaffected control subjects. Neuropathologic burden predicted less than 20% of the variance in psychosis status and did not account for the synaptic protein level differences between groups. Reduction of Kalrn in APPswe/PSEN1dE9 mice resulted in higher levels of synaptic proteins in cortical homogenate and normalized protein levels in the postsynaptic density.
conclusionsAccumulation of synaptic proteins, particularly those that are enriched in the postsynaptic density, is associated with resilience to psychosis in Alzheimer's disease. One candidate mechanism for this synaptic proteome compensation is alteration in levels of proteins that facilitate the transport of synaptic proteins to and from the postsynaptic density.
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