Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable
Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates,...
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2025-05-01
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| author | Rabab Al-Lahham Mark E. Corkins Mohd Ishtikhar Prakruti Rabadia Santiago Ramirez Victor Banerjee Mohammad Shahnawaz |
| author_facet | Rabab Al-Lahham Mark E. Corkins Mohd Ishtikhar Prakruti Rabadia Santiago Ramirez Victor Banerjee Mohammad Shahnawaz |
| author_sort | Rabab Al-Lahham |
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| description | Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients’ brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and MSA patients’ brains, as well as SAA-amplified α-Syn aggregates from LBD and MSA patients’ CSF samples, were used to treat synuclein biosensor cells, and induced intracellular α-Syn inclusions were analyzed by confocal microscopy. Our data indicate that induced α-Syn aggregates from LBD and MSA patients’ brains have similar seeding properties and morphological characteristics in the α-Syn biosensor cells as those amplified from LBD and MSA patients’ brains, as well as those amplified from LBD and MSA patients’ CSF samples. In this study, we demonstrated that, regardless of the source of aggregates, the seeds from LBD and MSA produce cellular accumulation of α-Syn with distinct morphologies, confirming the presence of different conformational strains of α-Syn in LBD and MSA and allowing us to differentiate synucleinopathies based on the morphology of aggregates and seeding properties. |
| format | Article |
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| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-21b30c9ca36c41d8bc36cf50c9d6ff6f2025-08-20T01:56:17ZengMDPI AGCells2073-44092025-05-01141068410.3390/cells14100684Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically IndistinguishableRabab Al-Lahham0Mark E. Corkins1Mohd Ishtikhar2Prakruti Rabadia3Santiago Ramirez4Victor Banerjee5Mohammad Shahnawaz6Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAMitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAMitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAMitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAMitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAMitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USALewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients’ brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and MSA patients’ brains, as well as SAA-amplified α-Syn aggregates from LBD and MSA patients’ CSF samples, were used to treat synuclein biosensor cells, and induced intracellular α-Syn inclusions were analyzed by confocal microscopy. Our data indicate that induced α-Syn aggregates from LBD and MSA patients’ brains have similar seeding properties and morphological characteristics in the α-Syn biosensor cells as those amplified from LBD and MSA patients’ brains, as well as those amplified from LBD and MSA patients’ CSF samples. In this study, we demonstrated that, regardless of the source of aggregates, the seeds from LBD and MSA produce cellular accumulation of α-Syn with distinct morphologies, confirming the presence of different conformational strains of α-Syn in LBD and MSA and allowing us to differentiate synucleinopathies based on the morphology of aggregates and seeding properties.https://www.mdpi.com/2073-4409/14/10/684Parkinson’s diseasemultiple system atrophyα-synucleinaggregationSAAbiosensor cells |
| spellingShingle | Rabab Al-Lahham Mark E. Corkins Mohd Ishtikhar Prakruti Rabadia Santiago Ramirez Victor Banerjee Mohammad Shahnawaz Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable Cells Parkinson’s disease multiple system atrophy α-synuclein aggregation SAA biosensor cells |
| title | Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable |
| title_full | Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable |
| title_fullStr | Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable |
| title_full_unstemmed | Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable |
| title_short | Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable |
| title_sort | intracellular inclusions induced by patient derived and amplified α synuclein aggregates are morphologically indistinguishable |
| topic | Parkinson’s disease multiple system atrophy α-synuclein aggregation SAA biosensor cells |
| url | https://www.mdpi.com/2073-4409/14/10/684 |
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