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Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease
Vlassenko AG, McCue L, Jasielec MS, Su Y, Gordon BA, Xiong C, Holtzman DM, Benzinger TL et al.. Annals of neurology, 2016-07-25
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Objective Deposition of amyloid β (Aβ)-containing plaques as evidenced by amyloid imaging and cerebrospinal fluid (CSF) Aβ1-42 (Aβ42) is an early indicator of preclinical Alzheimer disease (AD). To better understand their relationship during the earliest preclinical stages, we investigated baseline CSF markers in cognitively normal individuals at different stages of amyloid deposition defined by longitudinal amyloid imaging with Pittsburgh compound B (PIB): (1) PIB-negative at baseline and follow-up (PIB(-) ; normal), (2) PIB-negative at baseline but PIB-positive at follow-up (PIB converters; early preclinical AD), and (3) PIB-positive at baseline and follow-up (PIB(+) ; preclinical AD). Methods Cognitively normal individuals (n = 164) who had undergone baseline PIB scan and CSF collection within 1 year of each other and at least 1 additional PIB follow-up were included. Amyloid status was defined dichotomously using an a priori mean cortical cutoff. Results PIB converters (n = 20) at baseline exhibited significantly lower CSF Aβ42 compared to those who remained PIB-negative (n = 123), but higher compared to the PIB(+) group (n = 21). A robust negative correlation (r = -0.879, p = 0.0001) between CSF Aβ42 and absolute (but subthreshold) PIB binding was observed during this early preclinical stage. The negative correlation was not as strong once individuals were PIB-positive (r = -0.456, p = 0.038), and there was no correlation in the stable PIB(-) group (p = 0.905) or in the group (n = 10) with early symptomatic AD (p = 0.537). Interpretation CSF Aβ42 levels are tightly coupled with cortical amyloid load in the earliest stages of preclinical AD, and begin to decrease dramatically prior to the point when an abnormal threshold of cortical accumulation is detected with amyloid imaging. Ann Neurol 2016;80:379-387.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study of 164 participants. Among 164 cognitively normal people, those whose amyloid PET scan changed from negative to positive over follow-up had lower cerebrospinal fluid Aβ42 at baseline than those who stayed negative but higher than those already positive. This describes very early biomarker changes in preclinical Alzheimer's disease and does not test any treatment or prevention.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Vlassenko, A. G., McCue, L., Jasielec, M. S., Su, Y., Gordon, B. A., Xiong, C., et al. (2016). Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease. Annals of neurology. https://doi.org/10.1002/ana.24719
Vancouver
Vlassenko AG, McCue L, Jasielec MS, Su Y, Gordon BA, Xiong C, et al. Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease. Annals of neurology. 2016. doi:10.1002/ana.24719. PMID: 27398953.
BibTeX
@article{vlassenko2016-27398953,
author = {Vlassenko, A. G. and McCue, L. and Jasielec, M. S. and Su, Y. and Gordon, B. A. and Xiong, C. and Holtzman, D. M. and Benzinger, T. L. and others},
title = {{Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease}},
journal = {Annals of neurology},
year = {2016},
doi = {10.1002/ana.24719},
pmid = {27398953},
url = {https://doi.org/10.1002/ana.24719}
}
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Key findings
- Results PIB converters (n = 20) at baseline exhibited significantly lower CSF Aβ42 compared to those who remained PIB-negative (n = 123), but higher compared to the PIB(+) group (n = 21).
Why it matters
Among 164 cognitively normal people, those whose amyloid PET scan changed from negative to positive over follow-up had lower cerebrospinal fluid Aβ42 at baseline than those who stayed negative but higher than those already positive. This describes very early biomarker changes in preclinical Alzheimer's disease and does not test any treatment or prevention.
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Study details
- Study designlongitudinal study
- Participants164
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (OpenAlex, 2026-10-29) |
| 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 | 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 | 2 / 4 | 164 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 104 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.7 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 11.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Anne M. Fagan: h-index 122 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27398953) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
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