Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia

DeSimone, Jesse C.; Wang, Wei‐en; Loewenstein, David A.; Duara, Ranjan; Smith, Glenn E.; McFarland, Karen N.; Armstrong, Melissa J.; Weber, Darren M.; Barker, Warren; Coombes, Stephen A.; Vaillancourt, David E.

doi:10.1002/alz.13693

Cited by 2 publications

(1 citation statement)

References 77 publications

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“…We did not perform a detailed comparison with other biomarkers in the current study; instead, we focused on the utility of the plasma Aβ42/40 ratio biomarker in isolation. However, in a separate investigation, we show that early AD-related pathological changes in the Aβ42/40 biomarker were associated with quantifiable changes in brain microstructure and connectivity in Aβ-PET negative patients preceding deviations in other plasma biomarkers including t-tau, p-tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), and cortical atrophy ( 47 ).…”

Section: Discussionmentioning

confidence: 81%

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment

Weber,

Taylor,

Lagier

et al. 2024

Front. Neurol.

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IntroductionPlasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer’s disease (AD) assessment is unclear.MethodsAβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.ResultsHigh diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs. negative Aβ-PET results. Assuming a moderate prevalence of Aβ-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients’ cognitive impairment and help reduce PET evaluation by about 40%.ConclusionHigh-throughput plasma Aβ42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

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Section: Discussionmentioning

confidence: 81%

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment

Weber,

Taylor,

Lagier

et al. 2024

Front. Neurol.

Self Cite

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New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer’s disease risk assessment

Weber,

Kim,

Goldman

et al. 2024

Journal of Investigative Medicine

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Early detection of Alzheimer’s disease (AD) represents an unmet clinical need. Beta-amyloid (Aβ) plays an important role in AD pathology, and the Aβ42/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the 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 Aβ40 and Aβ42 quantitation, as well as apolipoprotein E (ApoE) phenotype determination as a surrogate for APOE genotype. Aβ40 and Aβ42 were simultaneously immunoprecipitated (IP) from plasma, proteolytically digested, and quantitated by LC-MS/MS. ApoE proteoform status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to CLIA guidelines. Within-run precision was 1.8 to 4.2% (Aβ40), 1.9 to 7.2% (Aβ42), and 2.6 to 8.3% (Aβ42/40 ratio). Between-run precision was 3.5 to 5.9% (Aβ40), 3.8 to 8.0% (Aβ42), and 3.3 to 8.7% (Aβ42/40 ratio). Both Aβ40 and Aβ42 were linear from 10 to 2,500 pg/mL. Identified ApoE proteoforms had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS/MS assay for plasma Aβ40, Aβ42, and proteoforms of ApoE.

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Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia

Cited by 2 publications

References 77 publications

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment

New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer’s disease risk assessment

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