{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:44:10Z","timestamp":1789015450441,"version":"build-2803163510"},"reference-count":27,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>Early detection of Alzheimer\u2019s disease (AD) represents an unmet clinical need. Beta-amyloid (A\u03b2) plays an important role in AD pathology, and the A\u03b242\/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the apolipoprotein E ( APOE) gene are associated with variable AD risk. Here, we describe the development and validation of high-throughput liquid chromatography-tandem mass spectrometry (LC-MS\/MS) assays for plasma A\u03b240 and A\u03b242 quantitation, as well as apolipoprotein E (ApoE) proteotype determination as a surrogate for APOE genotype. A\u03b240 and A\u03b242 were simultaneously immunoprecipitated from plasma, proteolytically digested, and quantitated by LC-MS\/MS. ApoE proteotype status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Within-run precision was 1.8%\u20134.2% (A\u03b240), 1.9%\u20137.2% (A\u03b242), and 2.6%\u20138.3% (A\u03b242\/40 ratio). Between-run precision was 3.5%\u20135.9% (A\u03b240), 3.8%\u20138.0% (A\u03b242), and 3.3%\u20138.7% (A\u03b242\/40 ratio). Both A\u03b240 and A\u03b242 were linear from 10 to 2500\u2009pg\/mL. Identified ApoE proteotypes had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS\/MS assay for plasma A\u03b240, A\u03b242, and proteoforms of ApoE.<\/jats:p>","DOI":"10.1177\/10815589241246537","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T22:51:47Z","timestamp":1711666307000},"page":"465-474","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["New plasma LC-MS\/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer\u2019s disease risk assessment"],"prefix":"10.1177","volume":"72","author":[{"given":"Darren M","family":"Weber","sequence":"first","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jueun C","family":"Kim","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M","family":"Goldman","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel J","family":"Clarke","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K","family":"Racke","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"bibr1-10815589241246537","first-page":"362","volume":"10","author":"Cummings J","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"key":"bibr2-10815589241246537","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.120618"},{"key":"bibr3-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.07.220"},{"key":"bibr4-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12179"},{"key":"bibr5-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.3180"},{"key":"bibr6-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15465"},{"key":"bibr7-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1038\/nature25456"},{"key":"bibr8-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00451-6"},{"key":"bibr9-10815589241246537","volume":"98","author":"Li Y","year":"2021","journal-title":"Neurology"},{"key":"bibr10-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"bibr11-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.8392"},{"key":"bibr12-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2021.05.011"},{"key":"bibr13-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01143-z"},{"key":"bibr14-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2016.256313"},{"key":"bibr15-10815589241246537","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2018.300947"},{"key":"bibr16-10815589241246537","volume-title":"Evaluation of precision of quantitative measurement procedures; approved guideline. 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