Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia
Yu L, Petyuk VA, Gaiteri C, Mostafavi S, Young-Pearse T, Shah RC, Buchman AS, Schneider JA et al.. Annals of neurology, 2018-07-03
Topic: Amyloid, tau and blood-test diagnosis
Objective Previous gene expression analysis identified a network of coexpressed genes that is associated with β-amyloid neuropathology and cognitive decline in older adults. The current work targeted influential genes in this network with quantitative proteomics to identify potential novel therapeutic targets. Methods Data came from 834 community-based older persons who were followed annually, died, and underwent brain autopsy. Uniform structured postmortem evaluations assessed the burden of β-amyloid and other common age-related neuropathologies. Selected reaction monitoring quantified cortical protein abundance of 12 genes prioritized from a molecular network of aging human brain that is implicated in Alzheimer's dementia. Regression and linear mixed models examined the protein associations with β-amyloid load and other neuropathological indices as well as cognitive decline over multiple years preceding death. Results Average age at death was 88.6 years. Overall, 349 participants (41.9%) had Alzheimer's dementia at death. A higher level of PLXNB1 abundance was associated with more β-amyloid load (p = 1.0 × 10 -7 ) and higher PHFtau tangle density (p = 2.3 × 10 -7 ), and the association of PLXNB1 with cognitive decline is mediated by these known Alzheimer's disease pathologies. On the other hand, higher IGFBP5, HSPB2, and AK4 and lower ITPK1 levels were associated with faster cognitive decline, and, unlike PLXNB1, these associations were not fully explained by common neuropathological indices, suggesting novel mechanisms leading to cognitive decline. Interpretation Using targeted proteomics, this work identified cortical proteins involved in Alzheimer's dementia and begins to dissect two different molecular pathways: one affecting β-amyloid deposition and another affecting resilience without a known pathological footprint. Ann Neurol 2018;83:78-88.
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APA 7th
Yu, L., Petyuk, V. A., Gaiteri, C., Mostafavi, S., Young-Pearse, T., Shah, R. C., et al. (2018). Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia. Annals of neurology. https://doi.org/10.1002/ana.25266
Vancouver
Yu L, Petyuk VA, Gaiteri C, Mostafavi S, Young-Pearse T, Shah RC, et al. Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia. Annals of neurology. 2018. doi:10.1002/ana.25266. PMID: 29908079.
BibTeX
@article{yu2018-29908079,
author = {Yu, L. and Petyuk, V. A. and Gaiteri, C. and Mostafavi, S. and Young-Pearse, T. and Shah, R. C. and Buchman, A. S. and Schneider, J. A. and others},
title = {{Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia}},
journal = {Annals of neurology},
year = {2018},
doi = {10.1002/ana.25266},
pmid = {29908079},
url = {https://doi.org/10.1002/ana.25266}
}
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Key findings
- Objective Previous gene expression analysis identified a network of coexpressed genes that is associated with β-amyloid neuropathology and cognitive decline in older adults.
- Results Average age at death was 88.6 years.
- Overall, 349 participants (41.9%) had Alzheimer's dementia at death.
- A higher level of PLXNB1 abundance was associated with more β-amyloid load (p = 1.0 × 10 -7 ) and higher PHFtau tangle density (p = 2.3 × 10 -7 ), and the association of PLXNB1 with cognitive decline is mediated by these known Alzheimer's disease pathologies.
- On the other hand, higher IGFBP5, HSPB2, and AK4 and lower ITPK1 levels were associated with faster cognitive decline, and, unlike PLXNB1, these associations were not fully explained by common neuropathological indices, suggesting novel mechanisms leading to cognitive decline.
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Study details
- Participants349
- Effect size41.9%
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 349 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29908079) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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