Selective effects of the APOE ε4 allele on presynaptic cholinergic markers in the neocortex of Alzheimer's disease
Open accessAbstract
The effects of the APOE epsilon4 allele on a range of pre- and postsynaptic cholinergic markers were studied in a cohort of community-based Alzheimer's disease (AD) patients. Compared with age-matched controls, the postmortem AD neocortex showed decreased choline acetyltransferase (ChAT) and acetyl cholinesterase activities, lower muscarinic M2, and nicotinic alpha4beta2 receptor densities, as well as reduced M1 receptor coupling to G-proteins. However, the epsilon4 allele was dose-dependently correlated only with higher losses of ChAT activities. AD patients with two epsilon4 alleles also had more beta-amyloid containing senile plaques in the temporal cortex compared to patients with 0/1 epsilon4. This study suggests that APOE epsilon4 selectively affects presynaptic cholinergic function which may contribute to the clinical and neuropathological features of AD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Presence of the ε4 allele correlates with a reduced number of dendritic spines in transgenic mice and AD patients.
“the presence of the 4 allele correlates with a reduced number of dendritic spines in transgenic mice and AD patients (Ji et al., 2003;Lai et al., 2006).”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Lai et al., 2006
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Garcia-Alloza, M., Gil-Bea, F. J., Diez-Ariza, M., Chen, C. P. L.-H., Francis, P. T., Lasheras, B., & Ramirez, M. J. (2005) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2004.06.007 · Cited by 244 · see citing works
Olichney, J. M., Hansen, L. A., Galasko, D., Saitoh, T., Hofstetter, C. R., Katzman, R., & Thal, L. J. (1996) · Neurology · doi:10.1212/wnl.47.1.190 · Cited by 216 · see citing works
Hardy, J. A., Wester, P., Winblad, B., Gezelius, C., Bring, G., & Eriksson, A. (1985) · Journal of Neural Transmission · doi:10.1007/bf01251916 · Cited by 185 · see citing works
White, F., Nicoll, J. A. R., Roses, A. D., & Horsburgh, K. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0401 · Cited by 128 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Self-citationAmyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
- Authors
- Lai, M. K. P., Tsang, S. W. Y., Garcia-Alloza, M., Minger, S. L., Nicoll, J. A. R., Esiri, M. M., Wong, P. T.-H., Chen, C. P. L.-H., Ramírez, M. J., & Francis, P. T.
- Affiliations
- King's College London (GB)
- National University of Singapore (SG)
- Southampton General Hospital (GB)
- University of Oxford (GB)
- Singapore General Hospital (SG)
- Centro de Investigación Médica Aplicada (ES)
- Corresponding author
- Lai, Mitchell K.P.
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 22
- Issue
- 3
- Pages
- 555-561
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W1970816926
- Cited by
- 29
- References
- 5
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2021: 2 · 2019: 3 · 2015: 2 · 2014: 2 · 2013: 1
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- European Social Fund
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- APOE ε4, Alzheimer's disease, choline acetyltransferase, acetylcholinesterase, M2 muscarinic receptor, neocortex, amyloid plaques, amyloid-beta, genetic risk
- MeSH terms
- Acetylcholine, Acetylcholinesterase, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Choline O-Acetyltransferase, Female, Genotype, Humans, Male, Receptors, Nicotinic, Biomarkers, Presynaptic Terminals, Neocortex, Receptor, Muscarinic M2, Receptor, Muscarinic M1, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
