Perivascular spaces as a potential biomarker of Alzheimer’s disease
Alzheimer’s disease (AD) is a highly damaging disease that affects one’s cognition and memory and presents an increasing societal and economic burden globally. Considerable research has gone into understanding AD; however, there is still a lack of effective biomarkers that aid in early diagnosis and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.1021131/full |
| _version_ | 1811341399766859776 |
|---|---|
| author | Miranda Lynch William Pham Benjamin Sinclair Benjamin Sinclair Benjamin Sinclair Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Meng Law Meng Law Meng Law Lucy Vivash Lucy Vivash Lucy Vivash Lucy Vivash |
| author_facet | Miranda Lynch William Pham Benjamin Sinclair Benjamin Sinclair Benjamin Sinclair Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Meng Law Meng Law Meng Law Lucy Vivash Lucy Vivash Lucy Vivash Lucy Vivash |
| author_sort | Miranda Lynch |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a highly damaging disease that affects one’s cognition and memory and presents an increasing societal and economic burden globally. Considerable research has gone into understanding AD; however, there is still a lack of effective biomarkers that aid in early diagnosis and intervention. The recent discovery of the glymphatic system and associated Perivascular Spaces (PVS) has led to the theory that enlarged PVS (ePVS) may be an indicator of AD progression and act as an early diagnostic marker. Visible on Magnetic Resonance Imaging (MRI), PVS appear to enlarge when known biomarkers of AD, amyloid-β and tau, accumulate. The central goal of ePVS and AD research is to determine when ePVS occurs in AD progression and if ePVS are causal or epiphenomena. Furthermore, if ePVS are indeed causative, interventions promoting glymphatic clearance are an attractive target for research. However, it is necessary first to ascertain where on the pathological progression of AD ePVS occurs. This review aims to examine the knowledge gap that exists in understanding the contribution of ePVS to AD. It is essential to understand whether ePVS in the brain correlate with increased regional tau distribution and global or regional Amyloid-β distribution and to determine if these spaces increase proportionally over time as individuals experience neurodegeneration. This review demonstrates that ePVS are associated with reduced glymphatic clearance and that this reduced clearance is associated with an increase in amyloid-β. However, it is not yet understood if ePVS are the outcome or driver of protein accumulation. Further, it is not yet clear if ePVS volume and number change longitudinally. Ultimately, it is vital to determine early diagnostic criteria and early interventions for AD to ease the burden it presents to the world; ePVS may be able to fulfill this role and therefore merit further research. |
| first_indexed | 2024-04-13T18:55:48Z |
| format | Article |
| id | doaj.art-cfc3f21bb8084888b0058b8b967317b0 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T18:55:48Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-cfc3f21bb8084888b0058b8b967317b02022-12-22T02:34:16ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-10-011610.3389/fnins.2022.10211311021131Perivascular spaces as a potential biomarker of Alzheimer’s diseaseMiranda Lynch0William Pham1Benjamin Sinclair2Benjamin Sinclair3Benjamin Sinclair4Terence J. O’Brien5Terence J. O’Brien6Terence J. O’Brien7Terence J. O’Brien8Meng Law9Meng Law10Meng Law11Lucy Vivash12Lucy Vivash13Lucy Vivash14Lucy Vivash15Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neurology, Alfred Hospital, Melbourne, VIC, AustraliaDepartment of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neurology, Alfred Hospital, Melbourne, VIC, AustraliaDepartment of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Radiology, Alfred Health, Melbourne, VIC, AustraliaDepartment of Electrical and Computer Systems Engineering, Monash University, Melbourne, VIC, AustraliaDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neurology, Alfred Hospital, Melbourne, VIC, AustraliaDepartment of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, AustraliaAlzheimer’s disease (AD) is a highly damaging disease that affects one’s cognition and memory and presents an increasing societal and economic burden globally. Considerable research has gone into understanding AD; however, there is still a lack of effective biomarkers that aid in early diagnosis and intervention. The recent discovery of the glymphatic system and associated Perivascular Spaces (PVS) has led to the theory that enlarged PVS (ePVS) may be an indicator of AD progression and act as an early diagnostic marker. Visible on Magnetic Resonance Imaging (MRI), PVS appear to enlarge when known biomarkers of AD, amyloid-β and tau, accumulate. The central goal of ePVS and AD research is to determine when ePVS occurs in AD progression and if ePVS are causal or epiphenomena. Furthermore, if ePVS are indeed causative, interventions promoting glymphatic clearance are an attractive target for research. However, it is necessary first to ascertain where on the pathological progression of AD ePVS occurs. This review aims to examine the knowledge gap that exists in understanding the contribution of ePVS to AD. It is essential to understand whether ePVS in the brain correlate with increased regional tau distribution and global or regional Amyloid-β distribution and to determine if these spaces increase proportionally over time as individuals experience neurodegeneration. This review demonstrates that ePVS are associated with reduced glymphatic clearance and that this reduced clearance is associated with an increase in amyloid-β. However, it is not yet understood if ePVS are the outcome or driver of protein accumulation. Further, it is not yet clear if ePVS volume and number change longitudinally. Ultimately, it is vital to determine early diagnostic criteria and early interventions for AD to ease the burden it presents to the world; ePVS may be able to fulfill this role and therefore merit further research.https://www.frontiersin.org/articles/10.3389/fnins.2022.1021131/fullperivascular space (PVS)glymphatic systemAlzheimer’s disease (AD)amyloid-betatauAPOE4 |
| spellingShingle | Miranda Lynch William Pham Benjamin Sinclair Benjamin Sinclair Benjamin Sinclair Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Terence J. O’Brien Meng Law Meng Law Meng Law Lucy Vivash Lucy Vivash Lucy Vivash Lucy Vivash Perivascular spaces as a potential biomarker of Alzheimer’s disease Frontiers in Neuroscience perivascular space (PVS) glymphatic system Alzheimer’s disease (AD) amyloid-beta tau APOE4 |
| title | Perivascular spaces as a potential biomarker of Alzheimer’s disease |
| title_full | Perivascular spaces as a potential biomarker of Alzheimer’s disease |
| title_fullStr | Perivascular spaces as a potential biomarker of Alzheimer’s disease |
| title_full_unstemmed | Perivascular spaces as a potential biomarker of Alzheimer’s disease |
| title_short | Perivascular spaces as a potential biomarker of Alzheimer’s disease |
| title_sort | perivascular spaces as a potential biomarker of alzheimer s disease |
| topic | perivascular space (PVS) glymphatic system Alzheimer’s disease (AD) amyloid-beta tau APOE4 |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.1021131/full |
| work_keys_str_mv | AT mirandalynch perivascularspacesasapotentialbiomarkerofalzheimersdisease AT williampham perivascularspacesasapotentialbiomarkerofalzheimersdisease AT benjaminsinclair perivascularspacesasapotentialbiomarkerofalzheimersdisease AT benjaminsinclair perivascularspacesasapotentialbiomarkerofalzheimersdisease AT benjaminsinclair perivascularspacesasapotentialbiomarkerofalzheimersdisease AT terencejobrien perivascularspacesasapotentialbiomarkerofalzheimersdisease AT terencejobrien perivascularspacesasapotentialbiomarkerofalzheimersdisease AT terencejobrien perivascularspacesasapotentialbiomarkerofalzheimersdisease AT terencejobrien perivascularspacesasapotentialbiomarkerofalzheimersdisease AT menglaw perivascularspacesasapotentialbiomarkerofalzheimersdisease AT menglaw perivascularspacesasapotentialbiomarkerofalzheimersdisease AT menglaw perivascularspacesasapotentialbiomarkerofalzheimersdisease AT lucyvivash perivascularspacesasapotentialbiomarkerofalzheimersdisease AT lucyvivash perivascularspacesasapotentialbiomarkerofalzheimersdisease AT lucyvivash perivascularspacesasapotentialbiomarkerofalzheimersdisease AT lucyvivash perivascularspacesasapotentialbiomarkerofalzheimersdisease |