Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age
Kok E, Haikonen S, Luoto T, Huhtala H, Goebeler S, Haapasalo H, Karhunen PJ.. Annals of neurology, 2009-06-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community-dwelling normal population. Methods This neuropathological study used both silver staining and A beta immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out-of-hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems. Results Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group. Interpretation The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Kok, E., Haikonen, S., Luoto, T., Huhtala, H., Goebeler, S., Haapasalo, H., et al. (2009). Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Annals of neurology. https://doi.org/10.1002/ana.21696
Vancouver
Kok E, Haikonen S, Luoto T, Huhtala H, Goebeler S, Haapasalo H, et al. Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Annals of neurology. 2009. doi:10.1002/ana.21696. PMID: 19557866.
BibTeX
@article{kok2009-19557866,
author = {Kok, E. and Haikonen, S. and Luoto, T. and Huhtala, H. and Goebeler, S. and Haapasalo, H. and Karhunen, P. J.},
title = {{Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age}},
journal = {Annals of neurology},
year = {2009},
doi = {10.1002/ana.21696},
pmid = {19557866},
url = {https://doi.org/10.1002/ana.21696}
}
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Key findings
- Results Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age.
- SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years).
- The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62).
- The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group.
- Interpretation The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.
Why it matters
In this autopsy study of a general population, amyloid plaques and tau tangles appeared from around age 30 and were more common in APOE epsilon 4 carriers, especially at ages 50 to 59. It describes when these brain changes begin and who is more likely to have them, but it does not test any treatment or prevention.
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Study details
- Participants603
- Effect size22.1%; 3.7%; 1.7%
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design and randomised / 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 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 603 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 | 6 / 7 | Cited 300 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.8 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 13.6× 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 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pekka J. Karhunen: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Tampere: institution h-index 544 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19557866) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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