Home › Research › Brain scans and imaging
Divergent amyloid trajectories distinguish normal aging from Alzheimer's disease progression
Tong M, Gao T, Upadhyaya Y, Nho K, Fang S, Saykin A, Yan J, for the Alzheimer's Disease Neuroimaging Initiative.. bioRxiv, 2026-09-14
Topic: Genetics and APOE
Aging is the greatest risk factor for Alzheimer's disease (AD), yet how and when AD-related pathological progression diverges from aging remains poorly understood. This distinction is particularly difficult at early stages, when clinically and biomarker-defined populations contain individuals following fundamentally different trajectories. Here, we model AD progression as a deviation from aging using longitudinal amyloid PET and a self-supervised trajectory-learning framework. In ADNI, the learned trajectory revealed a shared early path that bifurcated into an aging branch and an AD-related branch. The two branches showed distinct profiles in amyloid burden, cognitive decline, risk of progression to AD dementia, and genetic risk. Unseen participants from the independent NACC cohort were projected onto the trajectory without retraining, further reproducing key branch-specific biological and genetic patterns. Together, the bifurcating trajectory provides a biologically grounded framework for resolving early-stage heterogeneity and enabling risk stratification beyond binary amyloid status.
Key findings
- In ADNI, the learned trajectory revealed a shared early path that bifurcated into an aging branch and an AD-related branch.
New to this subject? Start with our plain-English guide: Brain scans & tests →
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 62 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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.
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
Tong, M., Gao, T., Upadhyaya, Y., Nho, K., Fang, S., Saykin, A., et al. (2026). Divergent amyloid trajectories distinguish normal aging from Alzheimer's disease progression. bioRxiv. https://doi.org/10.64898/2026.09.08.748727
Vancouver
Tong M, Gao T, Upadhyaya Y, Nho K, Fang S, Saykin A, et al. Divergent amyloid trajectories distinguish normal aging from Alzheimer's disease progression. bioRxiv. 2026. doi:10.64898/2026.09.08.748727.
BibTeX
@article{tong2026-20e069b5,
author = {Tong, M. and Gao, T. and Upadhyaya, Y. and Nho, K. and Fang, S. and Saykin, A. and Yan, J. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{Divergent amyloid trajectories distinguish normal aging from Alzheimer's disease progression}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.08.748727},
url = {https://doi.org/10.64898/2026.09.08.748727}
}
Related studies in Brain scans and imaging
Also tagged “convolutional”
205 studies in the library carry the topic tag “convolutional”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 205 tagged studies.