ArticleNeurobiology of disease2023
Unbiased classification of the elderly human brain proteome resolves distinct clinical and pathophysiological subtypes of cognitive impairment.
Article in Neurobiology of disease, 2023. 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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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Sleep fragmentation correlates with amyloid beta deposition at brain autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Associations of stable psychological traits with multi-omic subtypes of Alzheimer's dementia.Translational psychiatry · 2026Article
- Balanced deep learning on multi-omics networks identifies molecular subgroups of pathological brain aging.medRxiv : the preprint server for health sciences · 2026Article
- Multidomain therapy for Alzheimer's disease: a scoping review of cognitive decline trials.Molecular neurodegeneration · 2025Article
- Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Multi-scale integration of human brain vascular and CSF proteomes reveals biomarkers of cerebral amyloid angiopathy linked to Alzheimer's disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Brain wide engraftment of human monocytes induces neurodegeneration and cognitive dysfunction.Research square · 2025Article
- Cortical Gray Matter Proteins Associated With Cerebral Amyloid Angiopathy in Community-Dwelling Older Adults: An Autopsy Study.Neurology · 2025Article
- Benchmarking the AI-based diagnostic potential of plasma proteomics for neurodegenerative disease in 17,170 people.medRxiv : the preprint server for health sciences · 2025Article
- Synapse vulnerability and resilience across the clinical spectrum of dementias.Nature reviews. Neurology · 2025Review
- Multiplex Proteomics of Lewy Body Dementia Reveals Cerebrospinal Fluid Biomarkers of Disease Pathology and Progression.bioRxiv : the preprint server for biology · 2025Article
- Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer's disease.Nature aging · 2025Article
- Network analysis of the cerebrospinal fluid proteome reveals shared and unique differences between sporadic and familial forms of amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Article
- Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq.Nature biotechnology · 2025Article
- Translating the Post-Mortem Brain Multi-Omics Molecular Taxonomy of Alzheimer's Dementia to Living Humans.bioRxiv : the preprint server for biology · 2025Article
- Structural variants linked to Alzheimer's disease and other common age-related clinical and neuropathologic traits.Genome medicine · 2025Article
- Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Heparin-enriched plasma proteome is significantly altered in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Structural variants linked to Alzheimer's Disease and other common age-related clinical and neuropathologic traits.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Cognitive impairment in the elderly features complex molecular pathophysiology extending beyond the hallmark pathologies of traditional disease classification. Molecular subtyping using large-scale -omic strategies can help resolve this biological heterogeneity. Using quantitative mass spectrometry, we measured ∼8000 proteins across >600 dorsolateral prefrontal cortex tissues with clinical diagnoses of no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia. Unbiased classification of MCI and AD cases based on individual proteomic profiles resolved three classes with expression differences across numerous cell types and biological ontologies. Two classes displayed molecular signatures atypical of AD neurodegeneration, such as elevated synaptic and decreased inflammatory markers. In one class, these atypical proteomic features were associated with clinical and pathological hallmarks of cognitive resilience. We were able to replicate these classes and their clinicopathological phenotypes across two additional tissue cohorts. These results promise to better define the molecular heterogeneity of cognitive impairment and meaningfully impact its diagnostic and therapeutic precision.
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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.