Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain
<p>Abstract</p> <p>Background</p> <p>Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropa...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-11-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/4/1/46 |
| _version_ | 1819028615547846656 |
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| author | Liu Qiang Markesbery William R Schmitt Frederick A Peterson Shawn L Simmons Christopher R Furman Jennifer L Simpson James F Ling I-Fang Grear Karrie E Crook Julia E Younkin Steven G Bu Guojun Estus Steven |
| author_facet | Liu Qiang Markesbery William R Schmitt Frederick A Peterson Shawn L Simmons Christopher R Furman Jennifer L Simpson James F Ling I-Fang Grear Karrie E Crook Julia E Younkin Steven G Bu Guojun Estus Steven |
| author_sort | Liu Qiang |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).</p> <p>Results</p> <p>To identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform containing exon 2 showed that expression of FL-SORL1 was reduced in AD individuals. Moreover, FL-SORL1 was reduced in cognitively intact individuals with significant AD-like neuropathology. In contrast, the expression of the delta-2-SORL1 isoform was similar in AD and non-AD brains. The expression of FL-SORL1 was significantly associated with synaptophysin expression while delta-2-SORL1 was modestly enriched in white matter. Lastly, FL-SORL1 expression was associated with rs661057, a SORL1 intron one SNP that has been associated with AD risk. A linear regression analysis found that rs661057, synaptophysin expression and AD neuropathology were each associated with FL-SORL1 expression.</p> <p>Conclusion</p> <p>These results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain.</p> |
| first_indexed | 2024-12-21T06:01:11Z |
| format | Article |
| id | doaj.art-6fa12196c71042da82f08a63ef20f1c4 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-21T06:01:11Z |
| publishDate | 2009-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-6fa12196c71042da82f08a63ef20f1c42022-12-21T19:13:45ZengBMCMolecular Neurodegeneration1750-13262009-11-01414610.1186/1750-1326-4-46Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brainLiu QiangMarkesbery William RSchmitt Frederick APeterson Shawn LSimmons Christopher RFurman Jennifer LSimpson James FLing I-FangGrear Karrie ECrook Julia EYounkin Steven GBu GuojunEstus Steven<p>Abstract</p> <p>Background</p> <p>Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).</p> <p>Results</p> <p>To identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform containing exon 2 showed that expression of FL-SORL1 was reduced in AD individuals. Moreover, FL-SORL1 was reduced in cognitively intact individuals with significant AD-like neuropathology. In contrast, the expression of the delta-2-SORL1 isoform was similar in AD and non-AD brains. The expression of FL-SORL1 was significantly associated with synaptophysin expression while delta-2-SORL1 was modestly enriched in white matter. Lastly, FL-SORL1 expression was associated with rs661057, a SORL1 intron one SNP that has been associated with AD risk. A linear regression analysis found that rs661057, synaptophysin expression and AD neuropathology were each associated with FL-SORL1 expression.</p> <p>Conclusion</p> <p>These results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain.</p>http://www.molecularneurodegeneration.com/content/4/1/46 |
| spellingShingle | Liu Qiang Markesbery William R Schmitt Frederick A Peterson Shawn L Simmons Christopher R Furman Jennifer L Simpson James F Ling I-Fang Grear Karrie E Crook Julia E Younkin Steven G Bu Guojun Estus Steven Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain Molecular Neurodegeneration |
| title | Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain |
| title_full | Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain |
| title_fullStr | Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain |
| title_full_unstemmed | Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain |
| title_short | Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain |
| title_sort | expression of sorl1 and a novel sorl1 splice variant in normal and alzheimers disease brain |
| url | http://www.molecularneurodegeneration.com/content/4/1/46 |
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