Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease
Ikonomovic MD, Klunk WE, Abrahamson EE, Wuu J, Mathis CA, Scheff SW, Mufson EJ, DeKosky ST.. Neurology, 2011-06-22
Topic: Amyloid, tau and blood-test diagnosis
Objective This study examined the relationship between postmortem precuneus cholinergic enzyme activity, Pittsburgh compound B (PiB) binding, and soluble amyloid-β concentration in mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods Choline acetyltransferase (ChAT) activity, [(3)H]PiB binding, and soluble amyloid-β(1-42) (Aβ42) concentration were quantified in precuneus tissue samples harvested postmortem from subjects with no cognitive impairment (NCI), MCI, and mild AD and correlated with their last antemortem Mini-Mental State Examination (MMSE) score and postmortem pathologic evaluation according to the National Institute on Aging-Reagan criteria, recommendations of the Consortium to Establish a Registry for Alzheimer's Disease, and Braak stage. Results Precuneus ChAT activity was lower in AD than in NCI and was comparable between MCI and NCI. Precuneus [(3)H]PiB binding and soluble Aβ42 levels were elevated in MCI and significantly higher in AD than in NCI. Across all case subjects, reduced ChAT activity was associated with increased [(3)H]PiB binding, increased soluble Aβ42, lower MMSE score, presence of the APOE*4 allele, and more advanced AD pathology. Conclusions Despite accumulating amyloid burden, cholinergic enzyme activity is stable in the precuneus during prodromal AD. A decline in precuneus ChAT activity occurs only in clinical AD, when PiB binding and soluble Aβ42 levels are substantially elevated compared with those in MCI. Anti-amyloid interventions in MCI case subjects with a positive PiB PET scan may aid in reducing cholinergic deficits and cognitive decline later in the disease process.
Key findings
- Results Precuneus ChAT activity was lower in AD than in NCI and was comparable between MCI and NCI.
- Precuneus [(3)H]PiB binding and soluble Aβ42 levels were elevated in MCI and significantly higher in AD than in NCI.
- Across all case subjects, reduced ChAT activity was associated with increased [(3)H]PiB binding, increased soluble Aβ42, lower MMSE score, presence of the APOE*4 allele, and more advanced AD pathology.
- A decline in precuneus ChAT activity occurs only in clinical AD, when PiB binding and soluble Aβ42 levels are substantially elevated compared with those in MCI.
Why it matters
This postmortem study found that cholinergic enzyme activity in the precuneus was stable in mild cognitive impairment despite rising amyloid, and only declined in clinical Alzheimer's disease. Reduced enzyme activity was associated with more amyloid binding, lower cognitive scores, and the APOE*4 allele.
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Study details
- Evidence strengthLow
How this study scored 46/100
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 | 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 | 2011 — 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 | 4 / 7 | Cited 85 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 4.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 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 | 4 / 4 | Last-listed author Steven T. DeKosky: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21700583) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0b013e3182231419
- PubMed: 21700583
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Wuu, J., Mathis, C. A., Scheff, S. W., et al. (2011). Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0b013e3182231419
Vancouver
Ikonomovic MD, Klunk WE, Abrahamson EE, Wuu J, Mathis CA, Scheff SW, et al. Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology. 2011. doi:10.1212/wnl.0b013e3182231419. PMID: 21700583.
BibTeX
@article{ikonomovic2011-21700583,
author = {Ikonomovic, M. D. and Klunk, W. E. and Abrahamson, E. E. and Wuu, J. and Mathis, C. A. and Scheff, S. W. and Mufson, E. J. and DeKosky, S. T.},
title = {{Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease}},
journal = {Neurology},
year = {2011},
doi = {10.1212/wnl.0b013e3182231419},
pmid = {21700583},
url = {https://doi.org/10.1212/wnl.0b013e3182231419}
}
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