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Alzheimer's Disease: Genes, Proteins, and Therapy
Dennis J. Selkoe. Physiological Reviews, 2001-04-01
Topic: Amyloid, tau and blood-test diagnosis
Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid beta-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought gamma-secretase, coupled with the recent identification of beta-secretase, has provided discrete biochemical targets for drug screening and development. Alternate and novel strategies for inhibiting the early mechanism of the disease are also emerging. The progress reviewed here, coupled with better ability to diagnose the disease early, bode well for the successful development of therapeutic and preventative drugs for this major public health problem.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Selkoe, D. J. (2001). Alzheimer's Disease: Genes, Proteins, and Therapy. Physiological Reviews. https://doi.org/10.1152/physrev.2001.81.2.741
Vancouver
Selkoe DJ. Alzheimer's Disease: Genes, Proteins, and Therapy. Physiological Reviews. 2001. doi:10.1152/physrev.2001.81.2.741. PMID: 11274343.
BibTeX
@article{selkoe2001-11274343,
author = {Selkoe, Dennis J.},
title = {{Alzheimer's Disease: Genes, Proteins, and Therapy}},
journal = {Physiological Reviews},
year = {2001},
doi = {10.1152/physrev.2001.81.2.741},
pmid = {11274343},
url = {https://doi.org/10.1152/physrev.2001.81.2.741}
}
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Key findings
- All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid beta-protein in the brain.
- In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics.
- The finding that presenilin itself may be the long-sought gamma-secretase, coupled with the recent identification of beta-secretase, has provided discrete biochemical targets for drug screening and development.
- Alternate and novel strategies for inhibiting the early mechanism of the disease are also emerging.
- The progress reviewed here, coupled with better ability to diagnose the disease early, bode well for the successful development of therapeutic and preventative drugs for this major public health problem.
Why it matters
This review describes how inherited forms of Alzheimer's disease involve increased production or deposition of amyloid beta-protein, and how identifying the enzymes presenilin/gamma-secretase and beta-secretase provides targets for drug screening. It does not report a treatment or cure, but summarizes biological findings that could guide future therapeutic development.
Study details
- Evidence strengthLow
How this study scored 58/100
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 (Physiological Reviews) |
| Journal's citation record | 4 / 4 | Physiological Reviews: journal h-index 562 (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 | 2001 — 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 | 7 / 7 | Cited 6,067 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 224.7 citations a year over 27 year(s) since 2001 |
| Impact for its field and year | 4 / 6 | Cited 18.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 114 other studies in this library |
| Still being cited | 4 / 4 | Cited 360 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis J. Selkoe: h-index 174 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11274343) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
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