The genetic landscape of Alzheimer disease
Carmona S, Hardy J, Guerreiro R.. Handbook of clinical neurology, 2018-01-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD), a progressive and neurodegenerative disease, is the most common form of dementia with high incidence in elderly people. Neuropathologically the disease is defined by the combined presence of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles of phosphorylated tau protein. Genetically, the first clues were provided by genetic linkage studies that led to the identification of APP, PSEN1, and PSEN2 mutations as the main causes of autosomal-dominant early-onset AD. Another important hallmark was the identification of the APOE ɛ4 allele as a risk factor for late-onset AD. Over the last 20 years the development and implementation of new genetic and genomic technologies have allowed the identification of other genetic players in this disease. Genome-wide association studies identified more than 20 loci with common variability having small contributions to the susceptibility of AD. The majority of the genes mapped in these loci are known to be involved in specific biologic pathways: cholesterol metabolism, immune response, and endocytosis. More recently, the application of next-generation sequencing (mainly whole-exome sequencing) has begun to reveal the contribution of rarer variants with medium effects on risk for AD. This area of research has come a long way with many and important results allowing a better understanding of the disease. More efforts are still needed, however, to fully understand the etiology of this disease in order to establish reliable individual predictive models and put us closer to the development of a curative, preventive, or modulator drug.
Key findings
- This area of research has come a long way with many and important results allowing a better understanding of the disease.
Why it matters
This review describes how mutations in APP, PSEN1, and PSEN2 cause early-onset inherited Alzheimer disease and how APOE epsilon4 and more than 20 other gene regions contribute to late-onset risk. It summarizes genetic knowledge and does not report a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 48/100
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, so that was left out: it earned 46 of the 96 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Handbook of clinical 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 | 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 | 5 / 7 | Cited 134 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.4 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 6 / 6 | Cited 59.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rita João Guerreiro: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29478590) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 46 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 96 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Carmona, S., Hardy, J., & Guerreiro, R. (2018). The genetic landscape of Alzheimer disease. Handbook of clinical neurology. https://doi.org/10.1016/b978-0-444-64076-5.00026-0
Vancouver
Carmona S, Hardy J, Guerreiro R. The genetic landscape of Alzheimer disease. Handbook of clinical neurology. 2018. doi:10.1016/b978-0-444-64076-5.00026-0. PMID: 29478590.
BibTeX
@article{carmona2018-29478590,
author = {Carmona, S. and Hardy, J. and Guerreiro, R.},
title = {{The genetic landscape of Alzheimer disease}},
journal = {Handbook of clinical neurology},
year = {2018},
doi = {10.1016/b978-0-444-64076-5.00026-0},
pmid = {29478590},
url = {https://doi.org/10.1016/b978-0-444-64076-5.00026-0}
}
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