Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity
Hannah L Chandler, Carl J Hodgetts, Xavier Caseras, Kevin Murphy, Thomas M Lancaster. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020-01-02
Topic: Genetics and APOE
Preclinical models of Alzheimer's disease (AD) suggest APOE modulates brain function in structures vulnerable to AD pathophysiology. However, genome-wide association studies now demonstrate that AD risk is shaped by a broader polygenic architecture, estimated via polygenic risk scoring (AD-PRS). Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown. In a large sample (N = 608) of young, asymptomatic individuals, we measure the impact of both (i) APOE and (ii) AD-PRS on a vulnerable cortico-limbic scene-processing network heavily implicated in AD pathophysiology. Integrity of this network, which includes the hippocampus (HC), is fundamental for maintaining cognitive function during ageing. We show that AD-PRS, not APOE, selectively influences activity within the HC in response to scenes, while other perceptual nodes remained intact. This work highlights the impact of polygenic contributions to brain function beyond APOE, which could aid potential therapeutic/interventional strategies in the detection and prevention of AD.
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APA 7th
Chandler, H. L., Hodgetts, C. J., Caseras, X., Murphy, K., & Lancaster, T. M. (2020). Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. https://doi.org/10.1038/s41386-019-0595-1
Vancouver
Chandler HL, Hodgetts CJ, Caseras X, Murphy K, Lancaster TM. Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2020. doi:10.1038/s41386-019-0595-1. PMID: 31896120.
BibTeX
@article{chandler2020-31896120,
author = {Chandler, Hannah L and Hodgetts, Carl J and Caseras, Xavier and Murphy, Kevin and Lancaster, Thomas M},
title = {{Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity}},
journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
year = {2020},
doi = {10.1038/s41386-019-0595-1},
pmid = {31896120},
url = {https://doi.org/10.1038/s41386-019-0595-1}
}
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Key findings
- Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown.
- In a large sample (N = 608) of young, asymptomatic individuals, we measure the impact of both (i) APOE and (ii) AD-PRS on a vulnerable cortico-limbic scene-processing network heavily implicated in AD pathophysiology.
- Integrity of this network, which includes the hippocampus (HC), is fundamental for maintaining cognitive function during ageing.
- We show that AD-PRS, not APOE, selectively influences activity within the HC in response to scenes, while other perceptual nodes remained intact.
- This work highlights the impact of polygenic contributions to brain function beyond APOE, which could aid potential therapeutic/interventional strategies in the detection and prevention of AD.
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Study details
- Participants608
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / 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, multicenter collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology) |
| 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 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 608 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31896120) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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