Automated Assays Detecting Plasma Aβ42 and Aβ40 Are Predictive of Aβ Status in AD

Using fully automated Elecsys immunoassays, investigators found that plasma levels of the peptides Aβ1-42 (Aβ42) and Aβ1-40 (Aβ40) can predict levels of β-amyloid (Aβ) status in all stages of Alzheimer disease (AD), according to an article published in JAMA Neurology.

Investigators pooled data from 2 prospective, cross-sectional, multicenter studies: Swedish BioFINDER study between July 6, 2009, and February 11, 2015 (cohort 1, n=842); independent validation cohort between January 29, 2000 and October 11, 2006 (cohort 2, n=237). Participants in cohort 1 were classified as cognitively unimpaired (n=513), mild cognitive impairment (MCI, n=265), or AD dementia (n=64).

MCI and AD subgroups were combined as all participants with AD were Aβ positive and could not be examined separately using Aβ status as an outcome. Non-fasting blood samples and cerebrospinal fluid (CSF) were collected at the same time point, and analyzed according to a standardized protocol. Participants in the independent validation cohort were classified as cognitively unimpaired (n=34), MCI (n=109), or AD mild dementia (Mini-Mental State Examination score >22, n=94).

Of the 842 participants, 368 were positive for Aβ (prevalence, 44%); all 64 of those with AD dementia (100%), 157 of 265 of those with MCI (60%) and 147 of 513 of those with cognitive unimparment (29%) were positive for Aβ.

Positive correlations was found between all plasma and corresponding CSF biomarkers. In the BioFINDER cohort, plasma levels of Aβ42, Aβ40, and Aβ42/Aβ40 were decreased in Aβ-positive participants compared with Aβ-negative participants (Aβ42, P <.001; Aβ40, P =.003; Aβ42/Aβ42, P <.001). Plasma levels of Aβ42 were lower in cognitively unimpaired Aβ-positive, MCI Aβ-positive, and AD Aβ-positive dementia groups compared with the cognitively unimpaired Aβ-negative and MCI Aβ-negative groups when stratified by diagnostic subgroup (P <.001 for all).

Plasma Aβ42/Aβ40 ratio predicted Aβ positivity with an area under the curve (AUC) of 0.77 (95% confidence interval [CI], 0.74-0.81) in all participants in the BioFINDER group. Applying the BioFINDER model, which included plasma Aβ42, Aβ40, and tau in the validation cohort, the AUC was slightly lower than when using plasma Aβ42 and Aβ40 alone (AUC, 0.84; 95% CI, 0.79-0.89).

Limitations included lack of APOE data, lack of improvement when replicating the model that included plasma tau, and the small population size.

The researchers concluded that, “the most advantageous future use of optimized blood Aβ assays is as a screening tool for identifying subjects at a higher risk of being Aβ positive.” The believe such assays could be, “applied as an initial test together with other noninvasive, cost-efficient tools that aid the decision about whom a general practitioner should refer for further investigation at memory clinics where CSF or PET and more extensive clinical assessment could be used to support the AD diagnosis.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Palmqvist S, Janelidze S, Stomrud E, et al. Performance of fully automated plasma assays as screening tests for Alzheimer disease-related β-amyloid status [published online June 24, 2019]. JAMA Neurol. doi: 10.1001/jamaneurol.2019.1632