Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects
Chiang GC, Insel PS, Tosun D, Schuff N, Truran-Sacrey D, Raptentsetsang ST, Jack CR, Aisen PS et al.. Neurology, 2010-10-27
Topic: Brain proteins, microglia and lab models
Objective To determine whether elderly normal APOE E2 (APOE2) carriers exhibit slower rates of hippocampal atrophy and memory decline compared to APOE3/3 carriers. We also determined whether APOE2 carriers have less Alzheimer pathology as reflected by CSF biomarkers. Methods We included longitudinal data from 134 cognitively normal individuals (27 APOE2/2 or E2/3, 107 APOE3/3) from the Alzheimer's Disease Neuroimaging Initiative, a prospective cohort study. A linear mixed-effects model was used to determine how APOE2 affected rates of hippocampal atrophy and cognitive change over time. In a subsample of 72 individuals who also underwent CSF analysis, an ordinary least-squares regression was used to determine whether CSF β-amyloid (Aβ), total tau, and phosphorylated tau-181 (p-tau) differed by APOE2 status. Results APOE2 carriers demonstrated slower rates of hippocampal atrophy (p = 0.004). The mean rate of hippocampal atrophy among APOE2 carriers was -33 mm(3)/year (95% confidence interval -65 to +0.4), or -0.5%/year, compared to -86 mm(3)/year (95% confidence interval -102 to -71), or -1.3%/year, in the APOE3/3 group. No differences in the rates of episodic memory (p = 0.23) or overall cognitive change (p = 0.90) were detected. In the CSF subsample, APOE2 carriers had higher levels of CSF Aβ (p = 0.01), lower p-tau (p = 0.02), and marginally lower tau (p = 0.12). Conclusion A slower rate of hippocampal atrophy in normal APOE2 carriers is consistent with the lower risk of Alzheimer disease in these individuals. We hypothesize that the slower atrophy rate is related to decreased preclinical Alzheimer pathology.
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APA 7th
Chiang, G. C., Insel, P. S., Tosun, D., Schuff, N., Truran-Sacrey, D., Raptentsetsang, S. T., et al. (2010). Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects. Neurology. https://doi.org/10.1212/wnl.0b013e3181ffe4d1
Vancouver
Chiang GC, Insel PS, Tosun D, Schuff N, Truran-Sacrey D, Raptentsetsang ST, et al. Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects. Neurology. 2010. doi:10.1212/wnl.0b013e3181ffe4d1. PMID: 20980669.
BibTeX
@article{chiang2010-20980669,
author = {Chiang, G. C. and Insel, P. S. and Tosun, D. and Schuff, N. and Truran-Sacrey, D. and Raptentsetsang, S. T. and Jack, C. R. and Aisen, P. S. and others},
title = {{Hippocampal atrophy rates and CSF biomarkers in elderly APOE2 normal subjects}},
journal = {Neurology},
year = {2010},
doi = {10.1212/wnl.0b013e3181ffe4d1},
pmid = {20980669},
url = {https://doi.org/10.1212/wnl.0b013e3181ffe4d1}
}
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.
Key findings
- Objective To determine whether elderly normal APOE E2 (APOE2) carriers exhibit slower rates of hippocampal atrophy and memory decline compared to APOE3/3 carriers.
- Results APOE2 carriers demonstrated slower rates of hippocampal atrophy (p = 0.004).
- The mean rate of hippocampal atrophy among APOE2 carriers was -33 mm(3)/year (95% confidence interval -65 to +0.4), or -0.5%/year, compared to -86 mm(3)/year (95% confidence interval -102 to -71), or -1.3%/year, in the APOE3/3 group.
- No differences in the rates of episodic memory (p = 0.23) or overall cognitive change (p = 0.90) were detected.
- Conclusion A slower rate of hippocampal atrophy in normal APOE2 carriers is consistent with the lower risk of Alzheimer disease in these individuals.
Why it matters
In cognitively normal older adults, APOE2 carriers had slower rates of hippocampal atrophy and higher CSF amyloid and lower p-tau than APOE3/3 carriers, but no differences in memory or overall cognitive change were detected. This suggests APOE2 may be protective against some Alzheimer-related brain changes, but it does not show that any treatment can mimic this effect.
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Study details
- Study designcohort study
- Participants72
- Effect size0.5%; 1.3%
- Evidence strengthModerate
How this study scored 61/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 59 of the 96 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following 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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 72 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 93 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 5.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20980669) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 59 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 96 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0b013e3181ffe4d1
- PubMed: 20980669
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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