A landmark multinational study has successfully validated a blood test for diagnosing Alzheimer’s disease and frontotemporal lobar degeneration within diverse Latin American populations, addressing a critical disparity in dementia diagnostics. Historically, the science behind these promising blood tests was developed almost exclusively using data from North American and European cohorts, leaving their applicability in other genetically and socioeconomically diverse regions uncertain. This research, published in Nature Aging, confirms that specific plasma biomarkers can reliably differentiate between these devastating neurodegenerative conditions and cognitively normal individuals. This breakthrough arrives at a crucial time for Latin America, a region where dementia prevalence is projected to skyrocket from 8.5% to over 19% of individuals over 60 by 2050, affecting an estimated 12 million people and placing an immense strain on public health systems. The study represents the first large-scale, systematic effort to validate these accessible diagnostic tools in a region marked by unique demographic complexities.
Uncovering Distinct Pathological Signatures
The comprehensive analysis, co-led by Dr. Ariel Caviedes and Dr. Felipe Cabral-Miranda, involved 605 participants from Chile, Argentina, Brazil, Colombia, Peru, and Mexico, utilizing the established AT(N) biomarker framework. Researchers evaluated key blood-based markers including the amyloid-β 42/40 ratio (Aβ42/Aβ40), phosphorylated tau at positions 217 and 181 (p-tau217 and p-tau181), and neurofilament light chain (NfL). The findings revealed distinct pathological profiles for both Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). When compared against the cognitively normal control group, individuals with either form of dementia exhibited a reduced plasma Aβ42/Aβ40 ratio and elevated levels of p-tau217, p-tau181, and NfL. However, the crucial diagnostic distinctions emerged when comparing the two dementia types directly. P-tau217, a marker strongly associated with the dual amyloid and tau pathology of Alzheimer’s, was found to be significantly more elevated in individuals with AD than in those with FTLD.
In contrast to the Alzheimer’s-specific marker, neurofilament light chain (NfL), which serves as a general indicator of neuroaxonal injury, was found to be more pronounced in the FTLD group. This finding is consistent with the clinical presentation of FTLD, which is often characterized by a more rapid and widespread neurodegeneration compared to the typical progression of Alzheimer’s disease. To quantify the diagnostic capabilities of these biomarkers, the research team developed supervised machine learning models. These models achieved a high degree of accuracy, with a receiver operating characteristic area under the curve (ROC AUC) of 0.83 for distinguishing Alzheimer’s from controls and an even stronger AUC of 0.88 for separating FTLD from controls. The analysis identified p-tau217 as the single most powerful predictor for Alzheimer’s, while NfL proved to be the best individual predictor for FTLD. The established diagnostic cutoff for p-tau217 in AD (0.24 pg/mL) was remarkably similar to values reported in studies from high-income countries, suggesting its robustness across different populations.
The Power of an Integrated Diagnostic Approach
A central consensus emerging from the study is that the clinical value of blood biomarkers is maximized when they are not used in isolation but are integrated into a broader diagnostic framework. The researchers demonstrated strong and clinically meaningful correlations between the levels of these blood biomarkers and the specific clinical and neuroimaging findings associated with each disease. In the cohort of participants with Alzheimer’s disease, higher plasma levels of p-tau217 and NfL were directly linked to poorer performance on tests measuring executive function, global cognition, and the ability to perform activities of daily living. Furthermore, elevated p-tau217 specifically correlated with memory deficits, a finding that aligns perfectly with its known association with pathology in the hippocampus, the brain’s primary memory center. Neuroimaging data provided powerful corroboration, showing that abnormal biomarker levels corresponded to gray matter atrophy and reduced functional connectivity in classic Alzheimer’s-related brain regions, such as the temporo-parietal cortex and precuneus.
This multimodal strategy proved equally effective for the FTLD cohort. In this group, elevated levels of NfL and p-tau217 were primarily associated with executive dysfunction, a hallmark symptom of FTLD. Supporting these clinical observations, neuroimaging revealed atrophy in the orbitofrontal, insular, and anterior temporal regions of the brain, which are the areas known to be affected in the behavioral and language variants of FTLD. This integration of data significantly bolsters diagnostic confidence. When structural neuroimaging data was combined with the plasma biomarker results, the classification accuracy for Alzheimer’s against controls rose to 0.87, and for FTLD against controls, it reached an exceptional 0.95. This performance was enhanced even further by incorporating targeted neuropsychological measures into the models, resulting in final ROC AUCs of 0.90 for AD and 0.96 for FTLD. The most influential components in these comprehensive diagnostic models were p-tau217 levels, hippocampal volume, and measures of executive function, reinforcing that a holistic view provides the most accurate picture.
A Path Forward for Dementia Care in the Region
This pivotal study provided robust validation for the clinical application of blood-based AT(N) biomarkers in Latin America, demonstrating that plasma p-tau217 and NfL are effective tools for diagnosing and differentiating AD and FTLD in genetically and socioeconomically diverse populations. The research also shed light on the specific genetic landscape of the cohort, with 97.7% of participants having predominantly Amerindian ancestry. The presence of the APOE ε4 allele, a major genetic risk factor for AD, was associated with memory and functional decline specifically in the Alzheimer’s group, confirming its disease-specific effect within this population. While the study was limited by the absence of direct central nervous system measures like cerebrospinal fluid analysis or PET imaging for ultimate confirmation, it marked a crucial step toward democratizing dementia diagnosis. By providing a scalable, accessible, and validated method for early and accurate detection, these blood tests, when interpreted within a full clinical and imaging context, have the potential to transform dementia care and research in a region facing a significant and rapidly growing public health challenge.
