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Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling
Walker JM, Kazempour Dehkordi S, Fracassi A, Vanschoiack A, Pavenko A, Taglialatela G, Woltjer R, Richardson TE et al.. Acta neuropathologica communications, 2022-02-14
Topic: Brain proteins, microglia and lab models
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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APA 7th
Walker, J. M., Kazempour Dehkordi, S., Fracassi, A., Vanschoiack, A., Pavenko, A., Taglialatela, G., et al. (2022). Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling. Acta neuropathologica communications. https://doi.org/10.1186/s40478-022-01324-9
Vancouver
Walker JM, Kazempour Dehkordi S, Fracassi A, Vanschoiack A, Pavenko A, Taglialatela G, et al. Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling. Acta neuropathologica communications. 2022. doi:10.1186/s40478-022-01324-9. PMID: 35164877.
BibTeX
@article{walker2022-35164877,
author = {Walker, J. M. and Kazempour Dehkordi, S. and Fracassi, A. and Vanschoiack, A. and Pavenko, A. and Taglialatela, G. and Woltjer, R. and Richardson, T. E. and others},
title = {{Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling}},
journal = {Acta neuropathologica communications},
year = {2022},
doi = {10.1186/s40478-022-01324-9},
pmid = {35164877},
url = {https://doi.org/10.1186/s40478-022-01324-9}
}
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Key findings
- Previous studies have reported less overall neuronal loss, less gliosis, and fewer comorbidities in these individuals.
- 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 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.
Why it matters
Using spatial protein profiling in hippocampal tissue from 14 individuals, 11 proteins differed in tangle-bearing neurons between resilient and demented people. This is a small tissue study of protein expression patterns and does not test a treatment, cure or prevention.
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Study details
- Participants14
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 14 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 59 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 7.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Miranda E. Orr: h-index 30 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Oregon Health & Science University: institution h-index 1,025 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35164877) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
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