ArticleActa neuropathologica communications2022
Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Asymptomatic Versus Symptomatic Alzheimer's Disease Neuropathology: A Systematic Review of Differences Reported in Post-Mortem Studies.Neuropathology and applied neurobiology · 2026Pooled it
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Review
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology.Nature metabolism · 2025Article
- Primary age-related tauopathy.Acta neuropathologica · 2025Review
- Profiling lamina specific pyramidal neurons using postmortem human formalin fixed paraffin embedded frontal cortex tissue in combination with digital spatial profiling.Journal of neuroscience methods · 2025Article
- Cell-specific protein expression in Alzheimer's disease prefrontal cortex.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer's disease.Cell reports · 2025Article
- Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.Journal of neuropathology and experimental neurology · 2025Article
- Deciphering motor dysfunction and microglial activation in mThy1-Frontiers in molecular neuroscience · 2025Article
- Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia.NPJ dementia · 2025Article
- Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Biological mechanisms of resilience to tau pathology in Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Spatial proteomics: unveiling the multidimensional landscape of protein localization in human diseases.Proteome science · 2024Review
- Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.Neurobiology of disease · 2024Article
- Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer's disease.Acta neuropathologica · 2024Article
- Resistance and Resilience to Alzheimer's Disease.Cold Spring Harbor perspectives in medicine · 2024Review
- Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.Acta neuropathologica · 2024Article
- Spatial Multi-Omics in Alzheimer's Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression.Current issues in molecular biology · 2024Review
- Neuritic Plaques - Gateways to Understanding Alzheimer's Disease.Molecular neurobiology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Clinical symptoms correlate with underlying neurodegenerative changes in the vast majority of people. However, an intriguing group of individuals demonstrate neuropathologic changes consistent with Alzheimer disease (AD) yet remain cognitively normal (termed "resilient"). Previous studies have reported less overall neuronal loss, less gliosis, and fewer comorbidities in these individuals. Herein, NanoString GeoMx™ Digital Spatial Profiler (DSP) technology was utilized to investigate protein expression differences comparing individuals with dementia and AD neuropathologic change to resilient individuals. DSP allows for spatial analysis of protein expression in multiple regions of interest (ROIs) on formalin-fixed paraffin-embedded sections. ROIs in this analysis were hippocampal neurofibrillary tangle (NFT)-bearing neurons, non-NFT-bearing neurons, and their immediate neuronal microenvironments. Analyses of 86 proteins associated with CNS cell-typing or known neurodegenerative changes in 168 ROIs from 14 individuals identified 11 proteins displaying differential expression in NFT-bearing neurons of the resilient when compared to the demented (including APP, IDH1, CD68, GFAP, SYP and Histone H3). In addition, IDH1, CD68, and SYP were differentially expressed in the environment of NFT-bearing neurons when comparing resilient to demented. IDH1 (which is upregulated under energetic and oxidative stress) and PINK1 (which is upregulated in response to mitochondrial dysfunction and oxidative stress) both displayed lower expression in the environment of NFT-bearing neurons in the resilient. Therefore, the resilient display less evidence of energetic and oxidative stress. Synaptophysin (SYP) was increased in the resilient, which likely indicates better maintenance of synapses and synaptic connections. Furthermore, neurofilament light chain (NEFL) and ubiquitin c-terminal hydrolase (Park5) were higher in the resilient in the environment of NFTs. These differences all suggest healthier intact axons, dendrites and synapses in the resilient. In conclusion, resilient individuals display protein expression patterns suggestive of an environment containing less energetic and oxidative stress, which in turn results in maintenance of neurons and their synaptic connections.
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