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Alzheimer disease
David S. Knopman, Hélène Amieva, Ronald Carl Petersen, Gaël Chételat, David M. Holtzman, Bradley T. Hyman, Ralph A. Nixon, David Thomas Jones. Nature Reviews Disease Primers, 2021-05-13
Topic: Amyloid, tau and blood-test diagnosis
This Primer conceptualizes Alzheimer disease (AD) as a genetic and sporadic neurodegenerative disorder driven by a complex interplay between loss of synaptic homeostasis and endosomal/lysosomal clearance pathway dysfunction, in which Aβ and tau products play key roles. Clinically, AD presents with amnestic or non-amnestic cognitive impairment, and therapeutic efforts continue to struggle to identify targets within this framework that significantly alter its clinical course.
Key findings
- Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles.
- AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants.
- AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions.
- Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.
Why it matters
This Primer summarises how Alzheimer disease is defined by amyloid plaques and tau tangles, how it presents clinically, and the biological pathways thought to drive it. It notes that treatment efforts are still struggling to find targets that substantially change the course of the disease.
How this study scored 60/100
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 strength of evidence, so that was left out: it earned 57 of the 95 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature Reviews Disease Primers) |
| Journal's citation record | 3 / 4 | Nature Reviews Disease Primers: journal h-index 281 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 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 / 7 | Cited 2,493 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 356.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 6 / 6 | Cited 58.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 4 / 4 | Cited 1,750 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author David Thomas Jones: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33986301) |
| Free to read | 2 / 2 | Free to read |
| Points | 57 / 95 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 57 of the 95 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., et al. (2021). Alzheimer disease. Nature Reviews Disease Primers. https://doi.org/10.1038/s41572-021-00269-y
Vancouver
Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nature Reviews Disease Primers. 2021. doi:10.1038/s41572-021-00269-y. PMID: 33986301.
BibTeX
@article{knopman2021-33986301,
author = {Knopman, David S. and Amieva, Hélène and Petersen, Ronald Carl and Chételat, Gaël and Holtzman, David M. and Hyman, Bradley T. and Nixon, Ralph A. and Jones, David Thomas},
title = {{Alzheimer disease}},
journal = {Nature Reviews Disease Primers},
year = {2021},
doi = {10.1038/s41572-021-00269-y},
pmid = {33986301},
url = {https://doi.org/10.1038/s41572-021-00269-y}
}