Aug 2026· Frontiers in Neurology· Vol 17· 0 citations· 37 references
TL;DR
Among patients with isolated AD or isolated CSVD, plasma p-Tau217 is the optimal specific biomarker for the diagnosis of AD and differentiation between AD and cerebral small vessel disease.
Abstract
Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) are the two leading causes of cognitive impairment in the elderly, with overlapping clinical manifestations. This study aimed to explore the expression differences of plasma Aβ1-42, Aβ1-40, Aβ1-42/Aβ1-40, p-Tau181, p-Tau217, NfL and GFAP among patients with AD, CSVD and healthy populations, and to evaluate the diagnostic value of these biomarkers for AD as well as the differential diagnostic efficacy between AD and CSVD.
A total of 120 participants were enrolled and divided into AD group, CSVD group and healthy control group, with 40 cases in each group. Plasma biomarkers were detected by chemiluminescence immunoassay, and cognitive function and neuroimaging examinations were completed simultaneously. The differences of biomarker levels among the three groups were compared. Spearman correlation analysis was used to analyze the correlation between each biomarker and MMSE score, and ROC curve was adopted to evaluate the diagnostic and differential diagnostic efficacy of single biomarker.
Plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were significantly decreased, while p-Tau181 and p-Tau217 were markedly elevated in the AD group. The GFAP level in the CSVD group was specifically and significantly higher than that in the AD group and healthy control group. NfL was significantly increased in both disease groups. p-Tau217 exhibited optimal efficacy in distinguishing AD from healthy controls (AUC = 0.894) and differentiating AD from CSVD (AUC = 0.877). GFAP showed excellent diagnostic value in distinguishing CSVD from healthy controls (AUC = 0.881). All biomarkers were significantly correlated with MMSE scores.
Among patients with isolated AD or isolated CSVD, plasma p-Tau217 is the optimal specific biomarker for the diagnosis of AD and differentiation between AD and cerebral small vessel disease. GFAP acts as a key indicator for identifying CSVD. These findings should be interpreted cautiously for patients with AD-CSVD co-pathology. Combined detection of multiple plasma biomarkers provides an important clinical basis for non-invasive early screening and etiological classification of cognitive impairment in patients with pathologically isolated cognitive disorders.
In low- and middle-income countries, Alzheimer’s disease (AD) constitutes a growing public health burden. However, AD biomarkers research remains underrepresented in African populations. This study assesses core biomarkers of AD and their relevance in the African context as potential aid in clinical diagnosis. Nigerian older adults from VALIANT cohort (n = 967) underwent biomarker quantification in plasma (p-tau217, GFAP, NfL, Aβ42 and Aβ40) employing both the Single Molecule Assay (Simoa, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar). Biomarkers were associated with disease severity in clinical-diagnostic and clinical-biological groups, with stepwise increases of p-tau217, NfL and GFAP from cognitively unimpaired to dementia (p < 0.05). Results were consistent across platforms. Comparison between sexes showed higher biomarker levels in male participants across diagnostic groups. A significant effect of apoE-E4 proteotype on p-tau217 levels, after adjusting for age and sex was identified. These findings support the application of plasma AD biomarkers in the African context and the relevance of further AD biomarker research in diverse populations.
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A stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.
Keun You Kim, Hyunsun Ham, E. Yoon et al.· The journal of prevention of...· 0 citations
Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity, suggesting that both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.
Ahmed Kadom Kalaf, Khawla A. Shemran, Waleed Azeez AlAmeedy· International Journal of Nut...· 0 citations
In cognitively unimpaired older adults, elevated blood p-tau217 was linked to faster shrinkage in AD-specific brain regions, whereas NfL and GFAP were associated with more widespread atrophy, with NfL also associated with accelerated WMH accumulation.
Martina Valletta, D. L. Vetrano, E. Laukka et al.· Annals of Neurology· 0 citations
BackgroundBlood-based biomarkers (BBM) are promising to help diagnose Alzheimer's disease (AD) and are on the verge of implementation in diagnostic dementia workups. However, evaluating BBM performance in peripheral memory clinics is essential to establish their real-world clinical utility.ObjectiveTo evaluate the diagnostic concordance of BBMs with clinically established diagnoses in an unselected peripheral memory clinic population using predefined, validated thresholds.MethodsIn a peripheral memory clinic, plasma levels of phosphorylated Tau217 (pTau217), amyloid-β 42/40 ratio (Aβ42/Aβ40), glial fibrillary acidic protein, and neurofilament light (NfL) were measured in patients (mean age 75.2 ± 8.8 years, 48.3% female) clinically diagnosed with subjective cognitive decline (SCD; n = 108), mild cognitive impairment (MCI; n = 55), AD dementia (n = 132), or non-AD dementia (non-AD; n = 28). BBM levels were compared across diagnostic groups and concordance between clinical diagnoses and BBM test results, based on thresholds developed in an academic memory clinic, were analyzed.ResultsThe levels of all four BBMs differed between SCD and AD dementia (p < 0.001). Between AD dementia and non-AD dementia, only PTau217 levels differed (p = 0.03). In SCD participants, 50% (pTau217) to 79% (NfL) showed abnormality in at least one BBM. In AD dementia patients, this ranged from 83% (pTau217) to 97% (NfL); all had at least one abnormal BBM, and 68% had abnormalities in all four BBMs.ConclusionsIn a peripheral real-world memory clinic setting the BBMs demonstrated high concordance with clinically diagnosed dementia due to AD. Our findings suggest utility of BBMs in peripheral memory clinic practice, in patients with suspected dementia.
Marleen Kloppenburg-Lagendijk, Claire Van Nyendaal, Inge M. W. Verberk et al.· Journal of Alzheimer's Disea...· 0 citations