Can Blood Biomarkers for AD Predict Neurologic Outcomes After Cardiac Arrest?

Blood biomarkers indicative of Alzheimer disease (AD) rapidly changed in terms of dynamics and predictive value for future neurologic outcomes within the first 3 days following cardiac arrest, according to study findings published in JAMA Neurology.

Researchers conducted an international, prospective, clinical, biobank, and cohort study to analyze blood biomarkers in patients who experienced out-of-hospital cardiac arrests between November 11, 2010 and January 10, 2013. They obtained data on participants from the Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial.

They wanted to determine whether serum levels of biomarkers suggestive of AD, including blood phosphorylated tau (p-tau) and amyloid-β peptides 40 and 42 (Aβ40 and Aβ42), could effectively predict neurologic outcomes after cardiac arrest in patients with hypoxic-ischemic brain injury similar to biomarkers indicative of neural injury, such as neurofilament light (NfL) and total tau (t-tau).

Researchers divided the participants into 2 groups — 80 (86.25% men) into an initial discovery group and 717 (80.9% men) into the validation group. The mean age of the discovery cohort was 60.8, while the mean age of the validation group participants was 63.9.

Prospective collection of blood samples occurred 24, 48, and 72 hours following cardiac arrest and analyzed at later dates for specific biomarkers. NfL and t-tau were assessed between August 1 and 23, 2017. P-tau, Aβ40, and Aβ42 levels were assessed between July 1 and 15, 2021 and again between May 13 and 25, 2022.

Researchers divided the participants in the validation group into those with good neurologic outcomes (n=357) and those with poor neurologic outcomes (n=360). Good neurologic outcomes were defined as patients with scores of 2 or less on the Cerebral Performance Category scale, whereas poor neurologic outcomes were defined as patients with scores of 3 or higher on the Cerebral Performance Category scale.

Researchers further subdivided the patients in the good neurologic outcome group into those with low (<35 pg/mL) and high (>79 pg/mL) serum NfL levels, and the patients in the poor neurologic outcome group into those with low (<4212 pg/mL) and high (>4609 pg/mL) serum NfL levels.

In the discovery cohort, those with poor neurologic outcomes tended to be significantly older than those with good neurologic outcomes (62.8 years vs 58.8 years; P =.04). The researchers also observed a similar pattern in the validation cohort (68.0 years vs 59.9 years; P <.001).

Patients in the discovery cohort who eventually had poor neurologic outcomes demonstrated significant elevation in p-tau serum levels 24 hours after cardiac arrest. At 24 hours after cardiac arrest, no differences in the serum levels of Aβ40 and Aβ42 were observed between the poor and good neurologic outcome groups.

Serum p-tau levels 24 hours following cardiac arrest were highly predictive of neurologic outcomes 6 months later (area under the curve [AUC], 0.96; 95% CI, 0.95-0.97. P-tau demonstrated predictive values that were similar to serum NfL levels (AUC, 0.94; 95% CI, 0.92-0.96). In contrast, the predictive value of p-tau was significantly better than t-tau (AUC, 0.80; 95% CI, 0.77-0.84; P <.001) for neurologic outcomes 6 months following cardiac arrest.

As time went on, the predictive value of p-tau significantly decreased compared with t-tau and NfL at 48 and 72 hours after cardiac arrest. This rapid clearance of p-tau after 24 hours from insult suggested that this blood biomarker was not indicative of active, ongoing neuronal injury, an outcome better reflected by NfL levels.

In contrast, both at 48 hours and 72 hours after cardiac arrest, serum Aβ40 and Aβ42 levels were significantly elevated in those with poor neurologic outcomes; however, this association between these 2 blood biomarkers and neurologic outcomes was weak.

“Blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest,” the researchers noted. “The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of Aβ peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia,” they added.

Study limitations included the high number of p-tau and Aβ values in the validation cohort and the inability to determine if high p-tau levels actually predict AD onset within 24 hours following cardiac arrest. Additional limitations included the choice of immunoassay methods over mass spectrometry to calculate Aβ peptide levels.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.