CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers

CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers

Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further...

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Veröffentlicht in:Alzheimer's & dementia 2023-12, Vol.19 (S24), p.n/a
Hauptverfasser: Wilson, Rachael E, Jonaitis, Erin M., Langhough, Rebecca E, Betthauser, Tobey J, DiFilippo, Alexandra H, Christian, Bradley T., Okonkwo, Ozioma, Bendlin, Barbara B, Chin, Nathaniel A., Carlsson, Cynthia M, Asthana, Sanjay, Johnson, Sterling C, Zetterberg, Henrik
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container_issue S24
container_start_page
container_title Alzheimer's & dementia
container_volume 19
creator Wilson, Rachael E
Jonaitis, Erin M.
Langhough, Rebecca E
Betthauser, Tobey J
DiFilippo, Alexandra H
Christian, Bradley T.
Okonkwo, Ozioma
Bendlin, Barbara B
Chin, Nathaniel A.
Carlsson, Cynthia M
Asthana, Sanjay
Johnson, Sterling C
Zetterberg, Henrik
description Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further investigation is needed to determine the utility of this biomarker during the pre‐clinical phase. Method SNAP‐25 was measured using the Quanterix Single molecule array platform. A partial validation was conducted to evaluate assay performance in CSF and EDTA plasma. A cross‐sectional pilot study was then performed by measuring SNAP‐25 in CSF from 54 participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (WI‐ADRC) cohorts. SV2A synaptic density was measured in each participant using [11C]‐UCB‐J‐PET. Amyloid and tau status was determined in a subset of the group using [11C]‐PiB (N = 52) and [18F]‐MK6240‐PET (N = 44), respectively. Additional CSF biomarkers (Aß42, pTau‐181, and tTau) were measured using the Roche Cobas e601 Elecsys platform. A confirmatory study was performed with 80 additional WRAP and WI‐ADRC participants (53A+, 27 A‐). These participants did not have [11C]‐UCB‐J‐PET imaging. Result The SNAP‐25 assay demonstrated excellent precision (
doi_str_mv 10.1002/alz.082567
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fullrecord <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_alz_082567</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ALZ082567</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1137-8704e8ad950e40de8dba6c88ad4a5b7c19663c84851fb615af5a8549de6e19713</originalsourceid><addsrcrecordid>eNp9kM1Kw0AUhQdRsFY3PsGshdS5aWYyWabpj5WghbYbRcJkMqmjaVJmAiWufASf0SdxpMWli_vD5TuHy0HoGsgACPFvRfUxINynLDxBPaDU96gfRqd_OyPn6MLaN0ICwoH2kEyWU7x8iBffn18-xUljjKpEq5va4r1uX_Gyq8Wu1RKPVW112-G8w88AyYsTrJOR6_euFpMVnm_FRtcbLOoCx2M80s1WmHdl7CU6K0Vl1dVx9tF6Olkld176OJsncepJgGHo8ZAEiosiokQFpFC8yAWT3F0CQfNQQsTYUPKAUyhzBlSUVHAaRIViCqIQhn10c_CVprHWqDLbGe1-6DIg2W88mYsnO8TjYDjAe12p7h8yi9Ono-YHjK9pEA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers</title><source>Access via Wiley Online Library</source><creator>Wilson, Rachael E ; Jonaitis, Erin M. ; Langhough, Rebecca E ; Betthauser, Tobey J ; DiFilippo, Alexandra H ; Christian, Bradley T. ; Okonkwo, Ozioma ; Bendlin, Barbara B ; Chin, Nathaniel A. ; Carlsson, Cynthia M ; Asthana, Sanjay ; Johnson, Sterling C ; Zetterberg, Henrik</creator><creatorcontrib>Wilson, Rachael E ; Jonaitis, Erin M. ; Langhough, Rebecca E ; Betthauser, Tobey J ; DiFilippo, Alexandra H ; Christian, Bradley T. ; Okonkwo, Ozioma ; Bendlin, Barbara B ; Chin, Nathaniel A. ; Carlsson, Cynthia M ; Asthana, Sanjay ; Johnson, Sterling C ; Zetterberg, Henrik</creatorcontrib><description>Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further investigation is needed to determine the utility of this biomarker during the pre‐clinical phase. Method SNAP‐25 was measured using the Quanterix Single molecule array platform. A partial validation was conducted to evaluate assay performance in CSF and EDTA plasma. A cross‐sectional pilot study was then performed by measuring SNAP‐25 in CSF from 54 participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (WI‐ADRC) cohorts. SV2A synaptic density was measured in each participant using [11C]‐UCB‐J‐PET. Amyloid and tau status was determined in a subset of the group using [11C]‐PiB (N = 52) and [18F]‐MK6240‐PET (N = 44), respectively. Additional CSF biomarkers (Aß42, pTau‐181, and tTau) were measured using the Roche Cobas e601 Elecsys platform. A confirmatory study was performed with 80 additional WRAP and WI‐ADRC participants (53A+, 27 A‐). These participants did not have [11C]‐UCB‐J‐PET imaging. Result The SNAP‐25 assay demonstrated excellent precision (&lt;5% CV), recovery (96‐101%), and linearity in CSF. Plasma SNAP‐25 levels were detectable but inconsistent, suggesting matrix interference. In the pilot study, SNAP‐25 was highly correlated with CSF pTau‐181 and tTau (Figures 1A, 1B). SNAP‐25 was not correlated with CSF Aß42 (Figure 1C). A modest but significant correlation was observed with amyloid PET in the pilot study (Figure 2A) but not in the confirmatory study (Figure 3). SNAP‐25 did not correlate with SV2A density (Figure 2B) or fibrillary tau (Figure 2A). Mean SNAP‐25 levels were significantly different between amyloid‐ and tau‐positive groups compared to biomarker negative controls (p &lt; 0.001 for amyloid, p &lt; 0.05 for tau). Similar trends were observed in the confirmatory study (Figure 3). Conclusion These results demonstrate a close relationship between SNAP‐25 and soluble tau in CSF, suggesting that CSF SNAP‐25 reflects early Aß‐induced neuronal impairment in a way that correlates with tau pathophysiology. This indicates that SNAP‐25 could be a useful biomarker of early neurodegeneration in pre‐clinical AD.</description><identifier>ISSN: 1552-5260</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.082567</identifier><language>eng</language><ispartof>Alzheimer's &amp; dementia, 2023-12, Vol.19 (S24), p.n/a</ispartof><rights>2023 the Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falz.082567$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falz.082567$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids></links><search><creatorcontrib>Wilson, Rachael E</creatorcontrib><creatorcontrib>Jonaitis, Erin M.</creatorcontrib><creatorcontrib>Langhough, Rebecca E</creatorcontrib><creatorcontrib>Betthauser, Tobey J</creatorcontrib><creatorcontrib>DiFilippo, Alexandra H</creatorcontrib><creatorcontrib>Christian, Bradley T.</creatorcontrib><creatorcontrib>Okonkwo, Ozioma</creatorcontrib><creatorcontrib>Bendlin, Barbara B</creatorcontrib><creatorcontrib>Chin, Nathaniel A.</creatorcontrib><creatorcontrib>Carlsson, Cynthia M</creatorcontrib><creatorcontrib>Asthana, Sanjay</creatorcontrib><creatorcontrib>Johnson, Sterling C</creatorcontrib><creatorcontrib>Zetterberg, Henrik</creatorcontrib><title>CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers</title><title>Alzheimer's &amp; dementia</title><description>Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further investigation is needed to determine the utility of this biomarker during the pre‐clinical phase. Method SNAP‐25 was measured using the Quanterix Single molecule array platform. A partial validation was conducted to evaluate assay performance in CSF and EDTA plasma. A cross‐sectional pilot study was then performed by measuring SNAP‐25 in CSF from 54 participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (WI‐ADRC) cohorts. SV2A synaptic density was measured in each participant using [11C]‐UCB‐J‐PET. Amyloid and tau status was determined in a subset of the group using [11C]‐PiB (N = 52) and [18F]‐MK6240‐PET (N = 44), respectively. Additional CSF biomarkers (Aß42, pTau‐181, and tTau) were measured using the Roche Cobas e601 Elecsys platform. A confirmatory study was performed with 80 additional WRAP and WI‐ADRC participants (53A+, 27 A‐). These participants did not have [11C]‐UCB‐J‐PET imaging. Result The SNAP‐25 assay demonstrated excellent precision (&lt;5% CV), recovery (96‐101%), and linearity in CSF. Plasma SNAP‐25 levels were detectable but inconsistent, suggesting matrix interference. In the pilot study, SNAP‐25 was highly correlated with CSF pTau‐181 and tTau (Figures 1A, 1B). SNAP‐25 was not correlated with CSF Aß42 (Figure 1C). A modest but significant correlation was observed with amyloid PET in the pilot study (Figure 2A) but not in the confirmatory study (Figure 3). SNAP‐25 did not correlate with SV2A density (Figure 2B) or fibrillary tau (Figure 2A). Mean SNAP‐25 levels were significantly different between amyloid‐ and tau‐positive groups compared to biomarker negative controls (p &lt; 0.001 for amyloid, p &lt; 0.05 for tau). Similar trends were observed in the confirmatory study (Figure 3). Conclusion These results demonstrate a close relationship between SNAP‐25 and soluble tau in CSF, suggesting that CSF SNAP‐25 reflects early Aß‐induced neuronal impairment in a way that correlates with tau pathophysiology. This indicates that SNAP‐25 could be a useful biomarker of early neurodegeneration in pre‐clinical AD.</description><issn>1552-5260</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kM1Kw0AUhQdRsFY3PsGshdS5aWYyWabpj5WghbYbRcJkMqmjaVJmAiWufASf0SdxpMWli_vD5TuHy0HoGsgACPFvRfUxINynLDxBPaDU96gfRqd_OyPn6MLaN0ICwoH2kEyWU7x8iBffn18-xUljjKpEq5va4r1uX_Gyq8Wu1RKPVW112-G8w88AyYsTrJOR6_euFpMVnm_FRtcbLOoCx2M80s1WmHdl7CU6K0Vl1dVx9tF6Olkld176OJsncepJgGHo8ZAEiosiokQFpFC8yAWT3F0CQfNQQsTYUPKAUyhzBlSUVHAaRIViCqIQhn10c_CVprHWqDLbGe1-6DIg2W88mYsnO8TjYDjAe12p7h8yi9Ono-YHjK9pEA</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Wilson, Rachael E</creator><creator>Jonaitis, Erin M.</creator><creator>Langhough, Rebecca E</creator><creator>Betthauser, Tobey J</creator><creator>DiFilippo, Alexandra H</creator><creator>Christian, Bradley T.</creator><creator>Okonkwo, Ozioma</creator><creator>Bendlin, Barbara B</creator><creator>Chin, Nathaniel A.</creator><creator>Carlsson, Cynthia M</creator><creator>Asthana, Sanjay</creator><creator>Johnson, Sterling C</creator><creator>Zetterberg, Henrik</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>202312</creationdate><title>CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers</title><author>Wilson, Rachael E ; Jonaitis, Erin M. ; Langhough, Rebecca E ; Betthauser, Tobey J ; DiFilippo, Alexandra H ; Christian, Bradley T. ; Okonkwo, Ozioma ; Bendlin, Barbara B ; Chin, Nathaniel A. ; Carlsson, Cynthia M ; Asthana, Sanjay ; Johnson, Sterling C ; Zetterberg, Henrik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1137-8704e8ad950e40de8dba6c88ad4a5b7c19663c84851fb615af5a8549de6e19713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wilson, Rachael E</creatorcontrib><creatorcontrib>Jonaitis, Erin M.</creatorcontrib><creatorcontrib>Langhough, Rebecca E</creatorcontrib><creatorcontrib>Betthauser, Tobey J</creatorcontrib><creatorcontrib>DiFilippo, Alexandra H</creatorcontrib><creatorcontrib>Christian, Bradley T.</creatorcontrib><creatorcontrib>Okonkwo, Ozioma</creatorcontrib><creatorcontrib>Bendlin, Barbara B</creatorcontrib><creatorcontrib>Chin, Nathaniel A.</creatorcontrib><creatorcontrib>Carlsson, Cynthia M</creatorcontrib><creatorcontrib>Asthana, Sanjay</creatorcontrib><creatorcontrib>Johnson, Sterling C</creatorcontrib><creatorcontrib>Zetterberg, Henrik</creatorcontrib><collection>CrossRef</collection><jtitle>Alzheimer's &amp; dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wilson, Rachael E</au><au>Jonaitis, Erin M.</au><au>Langhough, Rebecca E</au><au>Betthauser, Tobey J</au><au>DiFilippo, Alexandra H</au><au>Christian, Bradley T.</au><au>Okonkwo, Ozioma</au><au>Bendlin, Barbara B</au><au>Chin, Nathaniel A.</au><au>Carlsson, Cynthia M</au><au>Asthana, Sanjay</au><au>Johnson, Sterling C</au><au>Zetterberg, Henrik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers</atitle><jtitle>Alzheimer's &amp; dementia</jtitle><date>2023-12</date><risdate>2023</risdate><volume>19</volume><issue>S24</issue><epage>n/a</epage><issn>1552-5260</issn><eissn>1552-5279</eissn><abstract>Background Synaptic dysfunction occurs prior to neuronal loss in the early stages of AD. A biomarker reflective of these changes could indicate AD before clinical manifestations. SNAP‐25 is a potential candidate, but the relationship between SNAP‐25 and established AD biomarkers is unclear. Further investigation is needed to determine the utility of this biomarker during the pre‐clinical phase. Method SNAP‐25 was measured using the Quanterix Single molecule array platform. A partial validation was conducted to evaluate assay performance in CSF and EDTA plasma. A cross‐sectional pilot study was then performed by measuring SNAP‐25 in CSF from 54 participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (WI‐ADRC) cohorts. SV2A synaptic density was measured in each participant using [11C]‐UCB‐J‐PET. Amyloid and tau status was determined in a subset of the group using [11C]‐PiB (N = 52) and [18F]‐MK6240‐PET (N = 44), respectively. Additional CSF biomarkers (Aß42, pTau‐181, and tTau) were measured using the Roche Cobas e601 Elecsys platform. A confirmatory study was performed with 80 additional WRAP and WI‐ADRC participants (53A+, 27 A‐). These participants did not have [11C]‐UCB‐J‐PET imaging. Result The SNAP‐25 assay demonstrated excellent precision (&lt;5% CV), recovery (96‐101%), and linearity in CSF. Plasma SNAP‐25 levels were detectable but inconsistent, suggesting matrix interference. In the pilot study, SNAP‐25 was highly correlated with CSF pTau‐181 and tTau (Figures 1A, 1B). SNAP‐25 was not correlated with CSF Aß42 (Figure 1C). A modest but significant correlation was observed with amyloid PET in the pilot study (Figure 2A) but not in the confirmatory study (Figure 3). SNAP‐25 did not correlate with SV2A density (Figure 2B) or fibrillary tau (Figure 2A). Mean SNAP‐25 levels were significantly different between amyloid‐ and tau‐positive groups compared to biomarker negative controls (p &lt; 0.001 for amyloid, p &lt; 0.05 for tau). Similar trends were observed in the confirmatory study (Figure 3). Conclusion These results demonstrate a close relationship between SNAP‐25 and soluble tau in CSF, suggesting that CSF SNAP‐25 reflects early Aß‐induced neuronal impairment in a way that correlates with tau pathophysiology. This indicates that SNAP‐25 could be a useful biomarker of early neurodegeneration in pre‐clinical AD.</abstract><doi>10.1002/alz.082567</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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title CSF SNAP‐25 Correlations with Synaptic Density by [11C]‐UCB‐J‐PET Imaging and AD Biomarkers
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