Novel blood-based biomarker may reliably detect Alzheimer’s-related brain abnormalities

Key takeaways:

• Higher placental growth factor was associated with a higher Clinical Dementia Rating score.
• The biomarker may be valuable for screening younger adults as an early Alzheimer’s intervention.

Placental growth factor, a blood-based protein, may be a reliable method to detect abnormalities in the brain that presage cognitive impairment indicative of Alzheimer’s disease, data show.

“Blood-based biomarkers are sorely needed to help diagnose and monitor patients at risk for vascular cognitive impairment, as, currently, brain MRI is the predominant method used for assessing a patient's burden of cerebrovascular disease,” Kyle C. Kern, MD, lead author of the study published in Alzheimer’s & Dementia and vascular neurologist at UCLA Health, told Healio in an email. “Placental growth factor is a promising blood-based biomarker that would be more cost-effective and accessible.”

A blood-based protein, placental growth factor (PlGF), may regulate cerebrovascular permeability and has the potential to be utilized as a biomarker to detect Alzheimer’s disease, Kern and colleagues wrote. They hypothesized that white-matter interstitial fluid accumulation, estimated by MRI imaging free water (FW), would clarify associations between elevated PlGF, white matter hyperintensities (WMH) in the brain and cognitive impairment indicative of disease presence.

Their cross-sectional study analyzed data of 370 older adults (mean age 72 years; 61% women; 83% white) from six sites across the Mark VCID consortium. The consortium was established to validate candidate biomarkers for cerebral small vessel disease by recruiting a diverse swath of candidates who possess a range of vascular risk factors and varied degrees of cognitive impairment. Records of all patients included testing for plasma PlGF as well as brain MRI.

Kyle C. Kern

All participants underwent a cognitive battery with the primary assessments being the Clinical Dementia Rating (CDR) and the Uniform Data Set version 3 composite of executive function (UDS3-EF).

Imaging across all study sites was performed with a trio of 3T MRI models, with researchers subsequently conducting a cross-sectional analysis of FW to determine if it mediated associations between PlGF and WMH, or PlGF and cognition, as measured by scores from CDR and UDS3-EF.

According to results, higher PlGF was associated with higher FW, higher WMH and higher CDR, but not UDS3-EF. Conversely, higher FW was associated with higher WMH and CDR, but lower UDS3-EF.

Kern and colleagues also reported that FW accounted for 26% of the association between PlGF and CDR, and 73% of that between PlGF and WMH.

Based on these data, the researchers suggested this biomarker may be valuable for screening younger adults as an early intervention to forestall potential vascular injury and cognitive decline.

“By demonstrating how elevated [placental growth factor] relates to MRI markers of cerebrovascular disease and worse cognitive status, this study bolsters our understanding of how [it] might be used clinically to diagnose or monitor vascular cognitive impairment,” Kern told Healio.

Reference:

Study supports new blood-based biomarker to detect early brain changes leading to cognitive impairment and dementia. https://www.uclahealth.org/news/release/study-supports-new-blood-based-biomarker-detect-early-brain. Published Dec. 18, 2024. Accessed Jan. 3, 2025.