Focal adhesions regulate Aβ signaling and cell death in Alzheimer's disease
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disorder that results from a loss of synaptic transmission and ultimately cell death. The presenting pathology of AD includes neuritic plaques composed of beta-amyloid peptide (Abeta) and neurofibrillary tangles composed of hyperphosphorylated tau, with neuronal loss in specific brain regions. However, the mechanisms that induce neuronal cell loss remain elusive. Focal adhesion (FA) proteins assemble into intracellular complexes involved in integrin-mediated communication between the extracellular matrix and the actin cytoskeleton, regulating many cell physiological processes including the cell cycle. Interestingly, recent studies report that integrins bind to Abeta fibrils, mediating Abeta signal transmission from extracellular sites of Abeta deposits into the cell and ultimately to the nucleus. In this review, we will discuss the Abeta induced integrin/FA signaling pathways that mediate cell cycle activation and cell death.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Multiple canonical focal adhesion signaling molecules are actively engaged in the AD brain.
“Interestingly, previous work has uncovered that multiple canonical focal ad hesion signaling molecules are actively engaged in the AD brain.”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Caltagarone et al., 2007
Section 3.1 reports MAPK activation in AD brain, and section 2.3 places paxillin in dystrophic neurites in human AD brain. But the paper's evidence that focal-adhesion molecules FAK and paxillin are phosphorylated comes from Aβ-treated cells and neurons in culture, not AD brain tissue. The claim extends that activation finding to multiple focal-adhesion molecules in the AD brain. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIntegrins bind Aβ and activate focal adhesion signaling.
“and integrins have been shown to bind Aβ and activate focal adhesion signaling (Caltagarone et al., 2007).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Caltagarone et al., 2007
Focal adhesions (FAs) regulate Aβ signalling.
“FAs have also been established as regulators of Aβ signalling [15]; however, the mechanistic details of the regulatory mechanisms are poorly understood, as are their potential links to the genetic component of the AD.”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Giancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869 · see citing works
Cheng, M., Sexl, V., Sherr, C. J., & Roussel, M. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1091 · Cited by 496 · see citing works
Grace, E. A., & Busciglio, J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-02-00493.2003 · Cited by 113 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- K. Jin, A.L. Peel, X.O. Mao, L. Xie, B.A. Cottrell, D.C. Henshall, D.A. Greenberg, Increased hippocampal neurogenesis in Alzheimer's disease, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 343-347.
- T. Hosaka, W.H. Biggs III, D. Tieu, A.D. Boyer, N.M. Varki, W.K. Cavenee, K.C. Arden, Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 2975-2980.
Cited by
Sorted by citations
Gupta, A., Bisht, B., & Dey, C. S. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.033 · Cited by 302 · see citing works
Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer’s Disease Genetics
Podleśny-Drabiniok, A., Marcora, E., & Goate, A. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.002 · Cited by 211 · see citing works
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J., & Lambert, J.-C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02004-0 · Cited by 168 · see citing works
Altered subcellular distribution of c-Abl in Alzheimer’s disease
Jing, Z., Caltagarone, J., & Bowser, R. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1062 · Cited by 83 · see citing works
Self-citationGong, Y., & Lippa, C. F. (2010) · American Journal of Alzheimer's Disease & Other Dementias® · doi:10.1177/1533317510382893 · Cited by 76 · see citing works
Saleh, B., Srikanth, K. D., Sneh, T., Yue, L., Pelech, S., Elliott, E., & Gil-Henn, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169055 · Cited by 10 · see citing works
Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis
Walsh, A. E., Davis, B. A., Samuels, J. D., Mills, W. A., Thanos, J. M., Johnson, A. M., Moore, K. A., Puchalski, M. A., Steacy, E. J., Wendell, B. W., et al. (2026) · Journal of Experimental Medicine · doi:10.1084/jem.20260104
- Authors
- Caltagarone, J., Jing, Z., & Bowser, R.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Bowser, Robert
- ORCID
- Bowser, Robert
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 1772
- Issue
- 4
- Pages
- 438-445
- ISSN
- 0925-4439 (ISSN-L)
- PMC
- PMC1876750
- OpenAlex
- W2114027579
- Cited by
- 102
- References
- 3
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 6 · 2012: 9
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS042724, R01NS042724)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, focal adhesions, integrins, neuronal cell death, cell cycle activation, extracellular matrix, actin cytoskeleton, tau hyperphosphorylation, neuritic plaques, integrin signaling
- MeSH terms
- Alzheimer Disease, Cell Adhesion, Cell Cycle, Cell Survival, Humans, Neurons, Transcription, Genetic, Signal Transduction, Integrins, Amyloid beta-Peptides, Cell Death
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
