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Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship
Nelson PT, Braak H, Markesbery WR.. Journal of neuropathology and experimental neurology, 2009-01-01
Topic: Amyloid, tau and blood-test diagnosis
Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensiveclinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.
Key findings
- Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration.
- We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy.
- There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD.
- For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function.
- We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.
Why it matters
This review argues that existing data support the idea that both amyloid plaques and neurofibrillary tangles contribute to cognitive impairment in Alzheimer's disease. It notes that the disease does not progress in a linear way and that some people with dementia lack these hallmark plaques and tangles, while some without cognitive impairment have severe Alzheimer-type pathology at autopsy.
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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 (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 2009 — within 20 year(s) of the newest study here |
| 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 645 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.9 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 15.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 35 other studies in this library |
| Still being cited | 3 / 4 | Cited 114 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author William R. Markesbery: h-index 124 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19104448) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1097/nen.0b013e3181919a48
- PubMed: 19104448
- Original source →
- Free full text: Journal of Neuropathology & Experimental Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009). Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. Journal of neuropathology and experimental neurology. https://doi.org/10.1097/nen.0b013e3181919a48
Vancouver
Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. Journal of neuropathology and experimental neurology. 2009. doi:10.1097/nen.0b013e3181919a48. PMID: 19104448.
BibTeX
@article{nelson2009-19104448,
author = {Nelson, P. T. and Braak, H. and Markesbery, W. R.},
title = {{Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship}},
journal = {Journal of neuropathology and experimental neurology},
year = {2009},
doi = {10.1097/nen.0b013e3181919a48},
pmid = {19104448},
url = {https://doi.org/10.1097/nen.0b013e3181919a48}
}
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