Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease
Balasa M, Gelpi E, Antonell A, Rey MJ, Sánchez-Valle R, Molinuevo JL, Lladó A, Neurological Tissue Bank/University of Barcelona/Hospital Clínic NTB/UB/HC Collaborative Group.. Neurology, 2011-05-01
Topic: Amyloid, tau and blood-test diagnosis
Objectives Early-onset Alzheimer disease (EOAD) diagnosis often represents a challenge because of the high frequency of atypical presentations. Our aim was to describe the clinical features, APOE genotype, and its pathologic correlations of neuropathologic confirmed EOAD. Methods Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD ( Results Forty cases were selected. Mean age at onset was 54.5 years (range 46-60). The mean disease duration was 11 years with a mean diagnostic delay of 3.1 years. A total of 37.5% had a nonmemory presentation. Behavioral/executive dysfunction was the most prevalent atypical presentation. Incorrect initial clinical diagnoses were common (53%) in patients with atypical presentations, but rare when anterograde amnesia was the presenting symptom (4%). The incorrect initial clinical diagnoses were 2 behavioral variant frontotemporal lobar degeneration, 2 normal pressure hydrocephalus, 1 semantic dementia, 1 primary progressive aphasia, 1 corticobasal degeneration, 1 pseudodementia with depression, and 1 unclassifiable dementia. APOE genotype was ε3/ε3 in 59%, with no significant differences between typical and atypical presentations. APOE ε4 was 3.3 times more frequent in subjects with family history of AD. A total of 97.5% of the cases presented advanced neurofibrillary pathology. A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate. Conclusion One third of patients with pathologic confirmed EOAD presented with atypical symptoms. Patients with EOAD with nonamnestic presentations often receive incorrect clinical diagnoses.
Key findings
- Methods Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD ( Results Forty cases were selected.
- APOE genotype was ε3/ε3 in 59%, with no significant differences between typical and atypical presentations.
- A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate.
Why it matters
In pathologically confirmed early-onset Alzheimer's disease, atypical presentations were common and often led to incorrect initial diagnoses, while APOE genotype did not differ significantly between typical and atypical presentations. APOE ε4 was more frequent in those with a family history of Alzheimer's disease.
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Study details
- Participants37
- Effect size37.5%; 97.5%
- Evidence strengthLow
How this study scored 54/100
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 (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 37 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 | 5 / 7 | Cited 155 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.1 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Albert Lladó: h-index 55 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat de Barcelona: institution h-index 1,049 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21576687) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Balasa, M., Gelpi, E., Antonell, A., Rey, M. J., Sánchez-Valle, R., Molinuevo, J. L., et al. (2011). Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0b013e31821a44dd
Vancouver
Balasa M, Gelpi E, Antonell A, Rey MJ, Sánchez-Valle R, Molinuevo JL, et al. Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease. Neurology. 2011. doi:10.1212/wnl.0b013e31821a44dd. PMID: 21576687.
BibTeX
@article{balasa2011-21576687,
author = {Balasa, M. and Gelpi, E. and Antonell, A. and Rey, M. J. and Sánchez-Valle, R. and Molinuevo, J. L. and Lladó, A.},
title = {{Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease}},
journal = {Neurology},
year = {2011},
doi = {10.1212/wnl.0b013e31821a44dd},
pmid = {21576687},
url = {https://doi.org/10.1212/wnl.0b013e31821a44dd}
}
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