CD2AP at the junction of nephropathy and Alzheimer’s disease
Abstract Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer’s disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. Recent studies have investigat...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Molecular Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s13024-025-00852-x |
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| author | Milene Vandal Mohsen Janmaleki Isabel Rea Colin Gunn Sotaro Hirai Jeff Biernaskie Justin Chun Grant Gordon Andrey Shaw Amir Sanati-Nezhad Gerald Pfeffer Frederic Calon Minh Dang Nguyen |
| author_facet | Milene Vandal Mohsen Janmaleki Isabel Rea Colin Gunn Sotaro Hirai Jeff Biernaskie Justin Chun Grant Gordon Andrey Shaw Amir Sanati-Nezhad Gerald Pfeffer Frederic Calon Minh Dang Nguyen |
| author_sort | Milene Vandal |
| collection | DOAJ |
| description | Abstract Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer’s disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. Recent studies have investigated the cell types and mechanisms by which CD2AP gene dosage contributes to the key pathological features of AD. This review summarizes the fundamental roles of CD2AP in mammalian cells and systems, discusses the novel pathogenic mechanisms focused on CD2AP in AD and highlights the necessity of incorporating biological sex in CD2AP research. Finally, the article draws important parallels between kidney and brain physiology based on vascular and molecular organization, links kidney disease to AD, and suggests the existence of a kidney-brain axis in AD centered on CD2AP. |
| format | Article |
| id | doaj-art-e41abf2405784f62a7a88c400ace72a9 |
| institution | OA Journals |
| issn | 1750-1326 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj-art-e41abf2405784f62a7a88c400ace72a92025-08-20T02:30:59ZengBMCMolecular Neurodegeneration1750-13262025-06-0120112210.1186/s13024-025-00852-xCD2AP at the junction of nephropathy and Alzheimer’s diseaseMilene Vandal0Mohsen Janmaleki1Isabel Rea2Colin Gunn3Sotaro Hirai4Jeff Biernaskie5Justin Chun6Grant Gordon7Andrey Shaw8Amir Sanati-Nezhad9Gerald Pfeffer10Frederic Calon11Minh Dang Nguyen12Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryDepartment of Medicine, Division of Nephrology, University of Calgary, Cumming School of MedicineDepartment of Physiology and Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, University of CalgaryDepartment of Research BiologyBioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryFaculté de Pharmacie, Université LavalDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryAbstract Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer’s disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. Recent studies have investigated the cell types and mechanisms by which CD2AP gene dosage contributes to the key pathological features of AD. This review summarizes the fundamental roles of CD2AP in mammalian cells and systems, discusses the novel pathogenic mechanisms focused on CD2AP in AD and highlights the necessity of incorporating biological sex in CD2AP research. Finally, the article draws important parallels between kidney and brain physiology based on vascular and molecular organization, links kidney disease to AD, and suggests the existence of a kidney-brain axis in AD centered on CD2AP.https://doi.org/10.1186/s13024-025-00852-xCD2APAlzheimerKidney-brain axisBrain-body interactionsNeurodegenerationSexual dimorphism |
| spellingShingle | Milene Vandal Mohsen Janmaleki Isabel Rea Colin Gunn Sotaro Hirai Jeff Biernaskie Justin Chun Grant Gordon Andrey Shaw Amir Sanati-Nezhad Gerald Pfeffer Frederic Calon Minh Dang Nguyen CD2AP at the junction of nephropathy and Alzheimer’s disease Molecular Neurodegeneration CD2AP Alzheimer Kidney-brain axis Brain-body interactions Neurodegeneration Sexual dimorphism |
| title | CD2AP at the junction of nephropathy and Alzheimer’s disease |
| title_full | CD2AP at the junction of nephropathy and Alzheimer’s disease |
| title_fullStr | CD2AP at the junction of nephropathy and Alzheimer’s disease |
| title_full_unstemmed | CD2AP at the junction of nephropathy and Alzheimer’s disease |
| title_short | CD2AP at the junction of nephropathy and Alzheimer’s disease |
| title_sort | cd2ap at the junction of nephropathy and alzheimer s disease |
| topic | CD2AP Alzheimer Kidney-brain axis Brain-body interactions Neurodegeneration Sexual dimorphism |
| url | https://doi.org/10.1186/s13024-025-00852-x |
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