Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context
Summary: Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000118 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573177981566976 |
|---|---|
| author | Kenneth Marek David S. Russell Luis Concha-Marambio Seung Ho Choi Danna Jennings Michael C. Brumm Christopher S. Coffey Ethan Brown John Seibyl Matthew Stern Claudio Soto Andrew Siderowf |
| author_facet | Kenneth Marek David S. Russell Luis Concha-Marambio Seung Ho Choi Danna Jennings Michael C. Brumm Christopher S. Coffey Ethan Brown John Seibyl Matthew Stern Claudio Soto Andrew Siderowf |
| author_sort | Kenneth Marek |
| collection | DOAJ |
| description | Summary: Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur. Methods: Data from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA. Findings: CSF α-syn SAA was positive in 48% (34/71) of hyposmic compared to 4% (1/25) of normosmic PARS participants (relative risk, 11.97; 95% CI, 1.73–82.95). Among α-syn SAA positive hyposmics 65% remained without a DAT deficit for up to four years follow-up. α-syn SAA positive hyposmics were at higher risk of having DAT deficit (12 of 34) compared to α-syn SAA negative hyposmics (4 of 37; relative risk, 3.26; 95% CI, 1.16–9.16), and 7 of 12 α-syn SAA positive hyposmics with DAT deficit developed symptoms consistent with synucleinopathy. Interpretation: Approximately fifty percent of PARS participants with hyposmia, easily detected using simple, widely available tests, have synuclein pathology detected by α-syn SAA. Approximately, one third (12 of 34) α-syn SAA positive hyposmic individuals also demonstrate DAT deficit. This study suggests a framework to investigate screening paradigms for synuclein pathology that could lead to design of therapeutic prevention studies in individuals without symptoms. Funding: The study was funded by the U.S. Department of Defense, the Helen Graham Foundation and the Michael J. Fox Foundation for Parkinson's Research. |
| format | Article |
| id | doaj-art-d6caec8e28934eadbae7e808490e223f |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-d6caec8e28934eadbae7e808490e223f2025-02-02T05:27:41ZengElsevierEBioMedicine2352-39642025-02-01112105567Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in contextKenneth Marek0David S. Russell1Luis Concha-Marambio2Seung Ho Choi3Danna Jennings4Michael C. Brumm5Christopher S. Coffey6Ethan Brown7John Seibyl8Matthew Stern9Claudio Soto10Andrew Siderowf11Institute for Neurodegenerative Disorders, New Haven, CT, USA; Corresponding author. Institute for Neurodegenerative Disorders, 60 Temple St, New Haven, CT 06510, USA.Institute for Neurodegenerative Disorders, New Haven, CT, USAResearch and Development Unit, Amprion, San Diego, CA, USADepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USADenali Therapeutics, South San Francisco, CA, USADepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USADepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USADepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USAInstitute for Neurodegenerative Disorders, New Haven, CT, USADepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADepartment of Neurology, University of Texas McGovern Medical School, Houston, TX, USADepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USASummary: Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur. Methods: Data from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA. Findings: CSF α-syn SAA was positive in 48% (34/71) of hyposmic compared to 4% (1/25) of normosmic PARS participants (relative risk, 11.97; 95% CI, 1.73–82.95). Among α-syn SAA positive hyposmics 65% remained without a DAT deficit for up to four years follow-up. α-syn SAA positive hyposmics were at higher risk of having DAT deficit (12 of 34) compared to α-syn SAA negative hyposmics (4 of 37; relative risk, 3.26; 95% CI, 1.16–9.16), and 7 of 12 α-syn SAA positive hyposmics with DAT deficit developed symptoms consistent with synucleinopathy. Interpretation: Approximately fifty percent of PARS participants with hyposmia, easily detected using simple, widely available tests, have synuclein pathology detected by α-syn SAA. Approximately, one third (12 of 34) α-syn SAA positive hyposmic individuals also demonstrate DAT deficit. This study suggests a framework to investigate screening paradigms for synuclein pathology that could lead to design of therapeutic prevention studies in individuals without symptoms. Funding: The study was funded by the U.S. Department of Defense, the Helen Graham Foundation and the Michael J. Fox Foundation for Parkinson's Research.http://www.sciencedirect.com/science/article/pii/S2352396425000118Parkinson’s diseaseBiomarkersDopamine transporter imagingProdromal |
| spellingShingle | Kenneth Marek David S. Russell Luis Concha-Marambio Seung Ho Choi Danna Jennings Michael C. Brumm Christopher S. Coffey Ethan Brown John Seibyl Matthew Stern Claudio Soto Andrew Siderowf Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context EBioMedicine Parkinson’s disease Biomarkers Dopamine transporter imaging Prodromal |
| title | Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context |
| title_full | Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context |
| title_fullStr | Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context |
| title_full_unstemmed | Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context |
| title_short | Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional studyResearch in context |
| title_sort | evidence for alpha synuclein aggregation in older individuals with hyposmia a cross sectional studyresearch in context |
| topic | Parkinson’s disease Biomarkers Dopamine transporter imaging Prodromal |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000118 |
| work_keys_str_mv | AT kennethmarek evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT davidsrussell evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT luisconchamarambio evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT seunghochoi evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT dannajennings evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT michaelcbrumm evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT christopherscoffey evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT ethanbrown evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT johnseibyl evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT matthewstern evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT claudiosoto evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext AT andrewsiderowf evidenceforalphasynucleinaggregationinolderindividualswithhyposmiaacrosssectionalstudyresearchincontext |