Blood-Based Biomarkers May Predict Alzheimer’s Disease Risk

blood test_TS
blood test_TS
Determining if a patient with subtle cognitive symptoms suffers from prodromal or preclinical Alzheimer disease (AD) and whether that patient will progress to AD dementia is a challenge. However, this determination is critically important in order to ascertain a correct and early diagnosis of AD. Researchers may have found one method that can help.

Blood-based biomarkers make it possible to measure neurofilament light (NfL), β amyloid ratio (Aβ42/Aβ40), and P-tau in patients with mild cognitive impairment to determine whether they have preclinical Alzheimer disease (AD) or will progress to AD in the future, according to a study published in Nature Medicine.

The study examined the accuracy of plasma P-tau in patients with mild cognitive symptoms in predicting future AD when combined with other accessible and non-invasive biomarkers.

The researchers used the BioFINDER study as the primary cohort. The cohort included 340 individuals with mild cognitive symptoms. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) study was the validation cohort and included 106 individuals with subjective cognitive decline and 437 with mild cognitive impairment. The primary outcome of the study was progression to AD within 4 years.

The researchers found that the best model to predict AD within 4 years included plasma P-tau217, the number of APOE ε4 alleles, executive function, memory function, cortical thickness and plasma NfL. This model resulted in an area under the curve (AUC) of 0.92 (95% CI 0.89–0.95). Removing plasma NfL resulted in similar model performance (ΔAIC < 2) and accuracy (AUC = 0.91, 95% CI 0.88–0.95), the researchers found.

The most notable increase in accuracy occurred when P-tau was combined with cognitive tests of memory and executive function and the APOE genotype.

There were some study limitations. Plasma Aβ42/Aβ40 was not available in a large-enough sample size in the ADNI study and could not be included in that cohort. In addition, the cognitive tests were limited. The researchers also could not rule out that a larger sample size would yield a significant difference.

The results of the study expand the possibilities for early AD diagnosis. It may also prove useful for recruiting individuals with early AD to clinical trials.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Palmqvist S, Tideman P, Cullen N, et al. Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med. Published online May 24, 2021. doi:10.1038/s41591-021-01348-z