Topic: Genetics and APOE
Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases, while the majority of cases are sporadic or show modest familial clustering. These cases are of late onset and likely result from the interaction of many genes and the environment. More than 30 loci have been implicated in AD by a combination of linkage, genome-wide association, and whole genome/exome sequencing. We have learned from these studies that perturbations in endolysosomal, lipid metabolism, and immune response pathways substantially contribute to sporadic AD pathogenesis. We review here current knowledge about functions of AD susceptibility genes, highlighting cells of the myeloid lineage as drivers of at least part of the genetic component in late-onset AD. Although targeted resequencing utilized for the identification of causal variants has discovered coding mutations in some AD-associated genes, a lot of risk variants lie in noncoding regions. Here we discuss the use of functional genomics approaches that integrate transcriptomic, epigenetic, and endophenotype traits with systems biology to annotate genetic variants, and to facilitate discovery of AD risk genes. Further validation in cell culture and mouse models will be necessary to establish causality for these genes. This knowledge will allow mechanism-based design of novel therapeutic interventions in AD and promises coherent implementation of treatment in a personalized manner.
Key findings
- These cases are of late onset and likely result from the interaction of many genes and the environment.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biological psychiatry) |
| 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 28666525) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Pimenova, A. A., Raj, T., & Goate, A. M. (2018). Untangling Genetic Risk for Alzheimer's Disease. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2017.05.014
Vancouver
Pimenova AA, Raj T, Goate AM. Untangling Genetic Risk for Alzheimer's Disease. Biological psychiatry. 2018. doi:10.1016/j.biopsych.2017.05.014. PMID: 28666525.
BibTeX
@article{pimenova2018-28666525,
author = {Pimenova, A. A. and Raj, T. and Goate, A. M.},
title = {{Untangling Genetic Risk for Alzheimer's Disease}},
journal = {Biological psychiatry},
year = {2018},
doi = {10.1016/j.biopsych.2017.05.014},
pmid = {28666525},
url = {https://doi.org/10.1016/j.biopsych.2017.05.014}
}
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