APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging
Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, Mintun MA.. Annals of neurology, 2010-01-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To examine interactions of apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging. Methods Two hundred forty-one cognitively normal individuals, aged 45-88 years, had cerebral amyloid imaging studies with Pittsburgh Compound-B (PIB). Of the 241 individuals, 168 (70%) also had cerebrospinal fluid (CSF) assays of amyloid-beta(42) (Abeta(42)), tau, and phosphorylated tau (ptau(181)). All individuals were genotyped for APOE. Results The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age-dependent manner from 0% at ages 45-49 years to 30.3% at 80-88 years. Reduced levels of CSF Abeta(42) appeared to begin earlier (18.2% of those aged 45-49 years) and increase with age in higher frequencies (50% at age 80-88 years) than elevations of MCBP. There was a gene dose effect for the APOE4 genotype, with greater MCBP increases and greater reductions in CSF Abeta(42) with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF Abeta(42) levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau(181). Interpretation Increasing cerebral Abeta deposition with age is the pathobiological phenotype of APOE4. The biomarker sequence that detects Abeta deposition may first be lowered CSF Abeta(42), followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD.
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APA 7th
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., et al. (2010). APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of neurology. https://doi.org/10.1002/ana.21843
Vancouver
Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of neurology. 2010. doi:10.1002/ana.21843. PMID: 20186853.
BibTeX
@article{morris2010-20186853,
author = {Morris, J. C. and Roe, C. M. and Xiong, C. and Fagan, A. M. and Goate, A. M. and Holtzman, D. M. and Mintun, M. A.},
title = {{APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging}},
journal = {Annals of neurology},
year = {2010},
doi = {10.1002/ana.21843},
pmid = {20186853},
url = {https://doi.org/10.1002/ana.21843}
}
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Key findings
- Results The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age-dependent manner from 0% at ages 45-49 years to 30.3% at 80-88 years.
Why it matters
In 241 people aged 45 to 88 with no memory problems, those carrying more copies of the APOE4 gene variant had more amyloid on brain scans and lower amyloid-beta 42 in spinal fluid, while APOE2 carriers showed no age-related rise in scan amyloid — but neither variant was linked to tau in the spinal fluid of the 168 people tested. Amyloid changes were more common at older ages (elevated scan readings in 0% of 45–49-year-olds versus 30.3% of 80–88-year-olds), and spinal-fluid changes appeared earlier, leading the authors to suggest the fluid test "may" detect amyloid before the scan does. This was a one-time comparison of different people, not a follow-up study, and it tested no treatment or prevention.
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Study details
- Participants241
- Effect size30.3%; 18.2%
- Evidence strengthLow
How this study scored 62/100
Published in a leading specialty journal. Scored zero for study design 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 | 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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 241 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 833 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 46.3 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 5 / 6 | Cited 29.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 110 other studies in this library |
| Still being cited | 3 / 4 | Cited 79 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Mark A. Mintun: h-index 131 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20186853) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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