Home › Research › Biomarkers
Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain
Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP, Albert MS, Hyman BT et al.. Neurology, 2004-03-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Background Pathologic changes in the Alzheimer disease (AD) brain occur in a hierarchical neuroanatomical pattern affecting cortical, subcortical, and limbic regions. Objective To define the time course of pathologic and biochemical changes-amyloid deposition, amyloid beta-peptide (Abeta) accumulation, neurofibrillary tangle (NFT) formation, synaptic loss, and gliosis-within the temporal association cortex of AD cases of varying disease duration, relative to control brains. Methods Stereologic assessments of amyloid burden and tangle density as well as ELISA-based measurements of Abeta, synaptophysin, and glial fibrillary acidic protein (GFAP) were performed in the superior temporal sulcus from a cohort of 83 AD and 26 nondemented control brains. Results Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid-extractable Abeta species, reduced levels of synaptophysin, and elevated levels of GFAP. In AD cases, the duration of dementia correlated with the degree of tangle formation, gliosis, and synaptic loss but not with any Abeta measures. Accumulation of Abeta, measured both neuropathologically and biochemically, was markedly increased in AD brains independent of disease duration, even in cases of short duration. Conclusions These data support distinct processes in the initiation and progression of AD pathology within the temporal cortex: Deposition of Abeta reaches a "ceiling" early in the disease process, whereas NFT formation, synaptic loss, and gliosis continue throughout the course of the illness.
What this study adds
Evidence grade: Moderate
In post-mortem tissue from one temporal-lobe region of 83 Alzheimer's and 26 control brains, amyloid was markedly increased even when dementia had been short, and its level did not vary with how long dementia had lasted. Tangles, synaptic loss (lower synaptophysin) and gliosis (higher GFAP) were all greater the longer the illness.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ingelsson, M., Fukumoto, H., Newell, K. L., Growdon, J. H., Hedley-Whyte, E. T., Frosch, M. P., et al. (2004). Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. https://doi.org/10.1212/01.wnl.0000115115.98960.37
Vancouver
Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP, et al. Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004. doi:10.1212/01.wnl.0000115115.98960.37. PMID: 15037694.
BibTeX
@article{ingelsson2004-15037694,
author = {Ingelsson, M. and Fukumoto, H. and Newell, K. L. and Growdon, J. H. and Hedley-Whyte, E. T. and Frosch, M. P. and Albert, M. S. and Hyman, B. T. and others},
title = {{Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain}},
journal = {Neurology},
year = {2004},
doi = {10.1212/01.wnl.0000115115.98960.37},
pmid = {15037694},
url = {https://doi.org/10.1212/01.wnl.0000115115.98960.37}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid-extractable Abeta species, reduced levels of synaptophysin, and elevated levels of GFAP.
Why it matters
In post-mortem tissue from one temporal-lobe region of 83 Alzheimer's and 26 control brains, amyloid was markedly increased even when dementia had been short, and its level did not vary with how long dementia had lasted. Tangles, synaptic loss (lower synaptophysin) and gliosis (higher GFAP) were all greater the longer the illness. The authors conclude that amyloid "reaches a 'ceiling' early" while the other damage continues. Each brain was measured once after death, so this is an association between people, not a cause-and-effect sequence, and no treatment was tested.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 665 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.7 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 9.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 69 other studies in this library |
| Still being cited | 3 / 4 | Cited 65 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michael C. Irizarry: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15037694) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
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.
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
69 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Biomarkers from nearby years
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.