Home › Research › Laboratory science
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek ES, Holtzman DM. Nature Neuroscience, 2015-06
Topic: Amyloid, tau and blood-test diagnosis
This widely cited review examined the long-running debate over whether amyloid or tau comes first in Alzheimer's disease. The authors argue that amyloid buildup is likely the initial trigger that starts the disease process 20-30 years before symptoms, but that tau pathology - which emerges later and closer to symptom onset - is what actually drives neurodegeneration and cognitive decline, calling tau amyloid's 'wingman.'
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Musiek, E. S., & Holtzman, D. M. (2015). Three dimensions of the amyloid hypothesis: time, space and 'wingmen'. Nature Neuroscience.
Vancouver
Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and 'wingmen'. Nature Neuroscience. 2015. PMID: 26007213.
BibTeX
@article{musiek2015-f2cb1175,
author = {Musiek, E. S. and Holtzman, D. M.},
title = {{Three dimensions of the amyloid hypothesis: time, space and 'wingmen'}},
journal = {Nature Neuroscience},
year = {2015},
pmid = {26007213}
}
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Autosomal-dominant Alzheimer's mutations that overproduce amyloid-beta cause the disease, while mutations that solely overproduce tau do not, supporting amyloid as an upstream trigger
- Amyloid plaques accumulate 20-30 years before symptom onset, while tau pathology emerges much closer to the onset of cognitive symptoms
- Tau-PET and tau-related neurodegeneration correlate more strongly with cognitive decline than amyloid-PET does
- The authors propose amyloid needs 'time, space, and wingmen' (like tau and neuroinflammation) to cause neurodegeneration, rather than acting alone
Why it matters
The authors argue amyloid buildup is the initial trigger starting the disease 20-30 years before symptoms, while tau emerges later and is what drives neurodegeneration and cognitive decline. This frames tau as the closer target for slowing decline, but it is a review of existing evidence rather than a new treatment result.
Study details
- Evidence strengthModerate
Limitations
This is a narrative review synthesizing existing genetic, biomarker, and animal-model data rather than a new dataset; the amyloid-first model it supports remains contested, especially given the modest clinical benefits of anti-amyloid drugs in trials.
How this study scored 37/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people, randomised / blinded and indexed in PubMed 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, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 62 points we could judge it on, which is 37 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Neuroscience) |
| 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 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 | 0 / 6 | No other study in this library cites it |
| 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 | 0 / 2 | No PubMed ID and no DOI — scores zero (not stated in the record — scored 0) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 62 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 62 points we could judge it on is 37 out of 100. |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Laboratory science
Also in Laboratory science
6 studies in the library are filed under Laboratory science with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Laboratory science hub.