Topic: Amyloid, tau and blood-test diagnosis
Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to clinically normal individuals (who do not meet criteria for either mild cognitive impairment or dementia) and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be reliably inferred from the clinical presentation. SNAP is present in ∼23% of clinically normal individuals aged >65 years and in ∼25% of mildly cognitively impaired individuals. APOE*ε4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-β biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field.
Key findings
- APOE*ε4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals.
Why it matters
This article describes suspected non-Alzheimer disease pathophysiology (SNAP), a biomarker pattern of normal amyloid-beta but abnormal neurodegeneration markers, present in about 23% of clinically normal people over 65 and about 25% of those with mild cognitive impairment. It is a conceptual and controversial biomarker category, not a treatment, cure, or prevention.
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Study details
- Evidence strengthLow
How this study scored 51/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (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 | 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 | 1 / 5 | 2016 — 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 | 6 / 7 | Cited 306 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.5 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 7.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 28 other studies in this library |
| Still being cited | 3 / 4 | Cited 65 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Stephanie J. B. Vos: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26782335) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Jack, C. R., Knopman, D. S., Chételat, G., Dickson, D., Fagan, A. M., Frisoni, G. B., et al. (2016). Suspected non-Alzheimer disease pathophysiology--concept and controversy. Nature reviews. Neurology. https://doi.org/10.1038/nrneurol.2015.251
Vancouver
Jack CR, Knopman DS, Chételat G, Dickson D, Fagan AM, Frisoni GB, et al. Suspected non-Alzheimer disease pathophysiology--concept and controversy. Nature reviews. Neurology. 2016. doi:10.1038/nrneurol.2015.251. PMID: 26782335.
BibTeX
@article{jack2016-26782335,
author = {Jack, C. R. and Knopman, D. S. and Chételat, G. and Dickson, D. and Fagan, A. M. and Frisoni, G. B. and Jagust, W. and others},
title = {{Suspected non-Alzheimer disease pathophysiology--concept and controversy}},
journal = {Nature reviews. Neurology},
year = {2016},
doi = {10.1038/nrneurol.2015.251},
pmid = {26782335},
url = {https://doi.org/10.1038/nrneurol.2015.251}
}
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