DOI: 10.1002/alz.075083 ISSN: 1552-5260

Associations of Beta‐amyloid and Alzheimer’s Disease Risk with Patient Age in Over 2,000 Plasma Specimens Analyzed by LC‐MS/MS

Darren M Weber, Jueun C Kim, Scott Goldman, Nigel J Clarke, Michael K Racke
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Beta‐amyloid (Aβ) plays an important role in Alzheimer’s disease (AD) pathology with Aβ42/40 ratio being an indicator amyloid deposition. Measurements have been performed using cerebrospinal fluid specimens, but now plasma assays are available as less invasive options. Our objective was to evaluate associations of age with Aβ40, Aβ42, and AD risk assessed using the Aβ42/40 ratio in >2,000 plasma specimens measured by LC‐MS/MS.


Results from plasma specimens submitted to our laboratory for AD risk assessment were used for this analysis. Both peptides were quantitated using a CLIA‐validated LC‐MS/MS assay, and the ratio of Aβ42 to Aβ40 (Aβ42/40) was calculated. Using a ratio cutoff of 0.160, individuals were categorized as being at higher risk (HR) of developing AD (Aβ42/40 <0.160) or lower risk (LR) of developing AD (Aβ42/40 ≥0.160).


Results from 2,235 specimens (58% female) were analyzed. Overall, 987 (44.2%) individuals were classified as being at HR for AD. An inverse relationship between age and the Aβ42/40 ratio (Spearman’s rho = ‐0.249, p <0.001) was observed; on average, the Aβ42/40 ratio decreased 3% per decade of age. Individuals who were HR for AD were older than those who were at LR for AD (mean [SD] age, 74.4 [9.0] vs. 69.2 [12.6], p <0.001). Aβ42 values were lower in the HR group compared to the LR group (38.5 [11.4] pg/mL vs. 44.7 [11.1] pg/mL, p <0.001), whereas Aβ40 values were higher in the HR individuals compared to LR (267.3 [76.3] pg/mL, vs. 245.9 [57.8] pg/mL, p <0.001). Both Aβ40 and Aβ42 values increased with age: on average, Aβ40 increased 7% per decade (Spearman’s rho = 0.415, p < 0.001), and Aβ42 increased 4% per decade (Spearman’s rho = 0.213, p < 0.001).


In this cohort, we found almost 45% of individuals were HR for AD based on Aβ42/40 ratio. With respect to patient age, we found significant associations with risk reflecting decreases in Aβ42/40 ratio in plasma. We also found increases of both Aβ40 and Aβ42 plasma concentrations with age but at different rates; the rate of increase was almost double for Aβ40 compared to Aβ42.

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