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Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype
Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, Dong LM, Jakes R et al.. Experimental neurology, 1994-02-01
Topic: Brain proteins, microglia and lab models
A genetic classification of Alzheimer disease(s) (AD) is presented. We describe a potential metabolic process in individuals who inherit apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) alleles, leading to increased risk and earlier age of onset of late-onset Alzheimer disease. Apolipoprotein E-epsilon 3 (apoE3) binds to tau protein, possibly slowing the initial rate of tau phosphorylation and self-assembly into paired helical filaments (PHFs); apoE4 does not bind tau.
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APA 7th
Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., et al. (1994). Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Experimental neurology. https://doi.org/10.1006/exnr.1994.1019
Vancouver
Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, et al. Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Experimental neurology. 1994. doi:10.1006/exnr.1994.1019. PMID: 8313935.
BibTeX
@article{strittmatter1994-8313935,
author = {Strittmatter, W. J. and Weisgraber, K. H. and Goedert, M. and Saunders, A. M. and Huang, D. and Corder, E. H. and Dong, L. M. and Jakes, R. and others},
title = {{Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype}},
journal = {Experimental neurology},
year = {1994},
doi = {10.1006/exnr.1994.1019},
pmid = {8313935},
url = {https://doi.org/10.1006/exnr.1994.1019}
}
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Key findings
- We describe a potential metabolic process in individuals who inherit apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) alleles, leading to increased risk and earlier age of onset of late-onset Alzheimer disease.
- Apolipoprotein E-epsilon 3 (apoE3) binds to tau protein, possibly slowing the initial rate of tau phosphorylation and self-assembly into paired helical filaments (PHFs); apoE4 does not bind tau.
- Tau promotes microtubule assembly and stabilizes microtubules; hyperphosphorylated tau does not bind, thereby destabilizing microtubules.
- Hyperphosphorylated tau may self-assemble into PHFs.
Why it matters
This paper presents a hypothesis that people who inherit APOE4 alleles may have a metabolic process leading to increased risk and earlier onset of late-onset Alzheimer's disease, and that apoE3 binds tau while apoE4 does not. It is a hypothesis about a possible mechanism and does not provide a treatment, cure, or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental neurology) |
| Journal's citation record | 3 / 4 | Experimental Neurology: journal h-index 271 (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 | 1994 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 433 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 34 year(s) since 1994 |
| Impact for its field and year | 6 / 6 | Cited 44.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Allen D. Roses: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8313935) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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