Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation
Park JS, Lee J, Jung ES, Kim MH, Kim IB, Son H, Kim S, Kim S et al.. Nature communications, 2019-07-12
Topic: Brain proteins, microglia and lab models
The role of brain somatic mutations in Alzheimer's disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood. The putatively pathogenic brain somatic mutations identified in 26.9% (14 of 52) of AD individuals are enriched in PI3K-AKT, MAPK, and AMPK pathway genes known to contribute to hyperphosphorylation of tau. We show that a pathogenic brain somatic mutation in PIN1 leads to a loss-of-function mutation. In vitro mimicking of haploinsufficiency of PIN1 aberrantly increases tau phosphorylation and aggregation. This study provides new insights into the genetic architecture underlying the pathogenesis of AD.
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APA 7th
Park, J. S., Lee, J., Jung, E. S., Kim, M. H., Kim, I. B., Son, H., et al. (2019). Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation. Nature communications. https://doi.org/10.1038/s41467-019-11000-7
Vancouver
Park JS, Lee J, Jung ES, Kim MH, Kim IB, Son H, et al. Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation. Nature communications. 2019. doi:10.1038/s41467-019-11000-7. PMID: 31300647.
BibTeX
@article{park2019-31300647,
author = {Park, J. S. and Lee, J. and Jung, E. S. and Kim, M. H. and Kim, I. B. and Son, H. and Kim, S. and others},
title = {{Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation}},
journal = {Nature communications},
year = {2019},
doi = {10.1038/s41467-019-11000-7},
pmid = {31300647},
url = {https://doi.org/10.1038/s41467-019-11000-7}
}
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Key findings
- The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood.
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Study details
- Participants52
- Effect size26.9%
- Evidence strengthLow
How this study scored 55/100
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 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| 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 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 52 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 31300647) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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