Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease
Abstract Background There is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer’s disease (AD). Synaptic dysfunction and loss occur early in AD and synaptic loss measured in the brain tissue and by PET are closely linked to cognitive decline, rend...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-022-01002-x |
| _version_ | 1818278456479186944 |
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| author | Pia Kivisäkk Becky C. Carlyle Thadryan Sweeney James P. Quinn Christopher E. Ramirez Bianca A. Trombetta Muriel Mendes Mary Brock Carrie Rubel Julie Czerkowicz Danielle Graham Steven E. Arnold |
| author_facet | Pia Kivisäkk Becky C. Carlyle Thadryan Sweeney James P. Quinn Christopher E. Ramirez Bianca A. Trombetta Muriel Mendes Mary Brock Carrie Rubel Julie Czerkowicz Danielle Graham Steven E. Arnold |
| author_sort | Pia Kivisäkk |
| collection | DOAJ |
| description | Abstract Background There is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer’s disease (AD). Synaptic dysfunction and loss occur early in AD and synaptic loss measured in the brain tissue and by PET are closely linked to cognitive decline, rendering synaptic proteins a promising target for biomarker development. Methods We used novel Simoa assays to measure cerebrospinal fluid (CSF) levels of two synaptic biomarker candidates, postsynaptic density protein 95 (PSD-95/DLG4), and the presynaptically localized synaptosomal-associated protein 25 (SNAP-25), as well as neurogranin (Ng), an established postsynaptic biomarker. CSF samples from two well-characterized cohorts (n=178 and n=156) were selected from banked samples obtained from diagnostic lumbar punctures containing subjects with amyloid-ß (Aß) positive AD, subjects with non-AD neurodegenerative diseases, subjects with other neurological conditions, and healthy controls (HC). Results All subjects had detectable CSF levels of PSD-95, SNAP-25, and Ng. CSF levels of PSD-95, SNAP-25, and Ng were all correlated, with the strongest correlation between the presynaptic SNAP-25 and the postsynaptic neurogranin. AD subjects had on average higher concentrations of all three synaptic markers compared to those with non-AD neurodegenerative diseases, other neurological disorders, and HCs. Increased CSF levels of PSD-95, SNAP-25, and Ng were, however, not specific for AD and were present in sporadic cases with inflammatory or vascular disorders as well. High CSF levels of PSD-95 were also observed in a few subjects with other neurodegenerative disorders. Conclusion The data establishes PSD-95 as a promising CSF marker for neurodegenerative disease synaptic pathology, while SNAP-25 and Ng appear to be somewhat more specific for AD. Together, these synaptic markers hold promise to identify early AD pathology, to correlate with cognitive decline, and to monitor responses to disease-modifying drugs reducing synaptic degeneration. |
| first_indexed | 2024-12-12T23:17:44Z |
| format | Article |
| id | doaj.art-0875729332a4453b9db8db01aebfdc94 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-12T23:17:44Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-0875729332a4453b9db8db01aebfdc942022-12-22T00:08:22ZengBMCAlzheimer’s Research & Therapy1758-91932022-04-0114111110.1186/s13195-022-01002-xIncreased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s diseasePia Kivisäkk0Becky C. Carlyle1Thadryan Sweeney2James P. Quinn3Christopher E. Ramirez4Bianca A. Trombetta5Muriel Mendes6Mary Brock7Carrie Rubel8Julie Czerkowicz9Danielle Graham10Steven E. Arnold11Department of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalQuanterix CorporationQuanterix CorporationBiogenBiogenBiogenDepartment of Neurology, Alzheimer’s Clinical and Translational Research Unit, Massachusetts General HospitalAbstract Background There is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer’s disease (AD). Synaptic dysfunction and loss occur early in AD and synaptic loss measured in the brain tissue and by PET are closely linked to cognitive decline, rendering synaptic proteins a promising target for biomarker development. Methods We used novel Simoa assays to measure cerebrospinal fluid (CSF) levels of two synaptic biomarker candidates, postsynaptic density protein 95 (PSD-95/DLG4), and the presynaptically localized synaptosomal-associated protein 25 (SNAP-25), as well as neurogranin (Ng), an established postsynaptic biomarker. CSF samples from two well-characterized cohorts (n=178 and n=156) were selected from banked samples obtained from diagnostic lumbar punctures containing subjects with amyloid-ß (Aß) positive AD, subjects with non-AD neurodegenerative diseases, subjects with other neurological conditions, and healthy controls (HC). Results All subjects had detectable CSF levels of PSD-95, SNAP-25, and Ng. CSF levels of PSD-95, SNAP-25, and Ng were all correlated, with the strongest correlation between the presynaptic SNAP-25 and the postsynaptic neurogranin. AD subjects had on average higher concentrations of all three synaptic markers compared to those with non-AD neurodegenerative diseases, other neurological disorders, and HCs. Increased CSF levels of PSD-95, SNAP-25, and Ng were, however, not specific for AD and were present in sporadic cases with inflammatory or vascular disorders as well. High CSF levels of PSD-95 were also observed in a few subjects with other neurodegenerative disorders. Conclusion The data establishes PSD-95 as a promising CSF marker for neurodegenerative disease synaptic pathology, while SNAP-25 and Ng appear to be somewhat more specific for AD. Together, these synaptic markers hold promise to identify early AD pathology, to correlate with cognitive decline, and to monitor responses to disease-modifying drugs reducing synaptic degeneration.https://doi.org/10.1186/s13195-022-01002-xAlzheimer’s diseaseBiomarkersCerebrospinal fluidSynaptic markersPSD-95SNAP-25 |
| spellingShingle | Pia Kivisäkk Becky C. Carlyle Thadryan Sweeney James P. Quinn Christopher E. Ramirez Bianca A. Trombetta Muriel Mendes Mary Brock Carrie Rubel Julie Czerkowicz Danielle Graham Steven E. Arnold Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease Alzheimer’s Research & Therapy Alzheimer’s disease Biomarkers Cerebrospinal fluid Synaptic markers PSD-95 SNAP-25 |
| title | Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease |
| title_full | Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease |
| title_fullStr | Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease |
| title_full_unstemmed | Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease |
| title_short | Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer’s disease |
| title_sort | increased levels of the synaptic proteins psd 95 snap 25 and neurogranin in the cerebrospinal fluid of patients with alzheimer s disease |
| topic | Alzheimer’s disease Biomarkers Cerebrospinal fluid Synaptic markers PSD-95 SNAP-25 |
| url | https://doi.org/10.1186/s13195-022-01002-x |
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