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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-06-01
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
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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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