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Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Dietmar Rudolf Thal, Udo Rüb, Mario Orantes, Heiko Braak. Neurology, 2002-06-25
Topic: Amyloid, tau and blood-test diagnosis
In the first of five phases in the evolution of beta-amyloidosis Abeta deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Abeta deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Abeta-deposition. The 17 clinically proven AD cases exhibit Abeta-phases 3, 4, or 5. The nine nondemented cases with AD-related Abeta pathology show Abeta-phases 1, 2, or 3. Abeta-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Abeta-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Abeta. There are also indications that clinically proven AD cases with full-blown beta-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Abeta pathology.
Key findings
- In the first of five phases in the evolution of beta-amyloidosis Abeta deposits are found exclusively in the neocortex.
- The second phase is characterized by the additional involvement of allocortical brain regions.
- In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Abeta deposits as well.
- Several brainstem nuclei become additionally involved in phase 4.
- Phase 5, finally, is characterized by cerebellar Abeta-deposition.
Why it matters
This study describes five phases in the evolution of beta-amyloidosis in the human brain, beginning in the neocortex and spreading hierarchically to allocortical regions, diencephalic nuclei, striatum, cholinergic nuclei, brainstem nuclei, and finally the cerebellum. The 17 clinically proven Alzheimer's disease cases exhibited phases 3, 4, or 5, while nine nondemented cases with Alzheimer's-related amyloid pathology showed phases 1, 2, or 3.
Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 59/100
Published in a leading specialty 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 | 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 | Design recorded as “clinical trial”, which our rubric does not rank (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 | 2002 — 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 3,499 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 134.6 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 9.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 6 / 6 | Cited by 206 other studies in this library |
| Still being cited | 4 / 4 | Cited 911 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Heiko Braak: h-index 121 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bonn: institution h-index 1,072 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12084879) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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. Check the citation against the original before you use it.
APA 7th
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002). Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology. https://doi.org/10.1212/wnl.58.12.1791
Vancouver
Thal DR, Rüb U, Orantes M, Braak H. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology. 2002. doi:10.1212/wnl.58.12.1791. PMID: 12084879.
BibTeX
@article{thal2002-12084879,
author = {Thal, Dietmar Rudolf and Rüb, Udo and Orantes, Mario and Braak, Heiko},
title = {{Phases of Aβ-deposition in the human brain and its relevance for the development of AD}},
journal = {Neurology},
year = {2002},
doi = {10.1212/wnl.58.12.1791},
pmid = {12084879},
url = {https://doi.org/10.1212/wnl.58.12.1791}
}
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