The findings identify a group of peripheral inflammatory markers associated with AD pathology and suggest that some of these relationships may vary by sex, warranting larger studies to clarify the role of sex in AD pathobiology.
Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative illness characterised by aberrant protein accumulation and progressive cognitive decline. One of the most researched blood indicators of tau pathology is phosphorylated tau 217 (p-tau217), and apolipoprotein E (ApoE) is essential for lipid metabolism, amyloid removal, and neuronal maintenance. The severity of AD may be correlated with changes in these biomarkers. Objective: To compare serum levels of p-tau217 and ApoE in individuals with different severities of Alzheimer's Disease. Methods: The present case–control study consisted of 156 subjects aged between 55 and 85 years:106 patients with ad (and balanced frequency matched to healthy controls on age, international classification of diseases t63 diagnosis). The DSM-5 criteria classified the patients as mild (n = 12), moderate (n = 50), or severe (n = 44). Using the sandwich enzyme-linked immunosorbent assay (ELISA), the levels of circulating ApoE and p-tau217 were determined. The receiver operating characteristics (ROC) curve examination, Spearman's correlation, and the Kruskal-Wallis test were used in the statistical studies. Results: The mean serum p-tau217 and ApoE level were 165 ± 84.2 pg/mL and 75.5 ± 55.6 ng/mL, respectively. While serum p-tau217 significantly increased with severity of disease, ApoE levels decreased. We found a significant positive association of p-tau217 (p<0.001) and a negative association of ApoE (p<0.001) with disease severity by DSM-5 criteria. ROC analysis showed high diagnostic accuracy of CSF p-tau217 (AUC=0.916, sensitivity: 87.18%, specificity: 90.00%) and ApoE (AUC=0.992, sensitivity: 100.00%, specificity:98.00%). Conclusion: Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity. Both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.
Objectives: The study objective is to reveal biochemical way to diagnose and know Alzheimer's patients biochemically instead of using traditional
Methods that used to diagnosis as an example using: Electroencephalography (EEG), computed tomography (CT), magnetic resonance imaging (MRI) and brain biopsy.
Methods: A case control research design was applied to current study, 156 individuals and thy were as follows: 12 with mild symptoms ,50 with moderate,44 with sever progression and 50 apparently as healthy control with an age range of 55 to 85 years were included. Samples were collected in accordance with the consultant's diagnosis; disease severity was categorized according to DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) staging, which was then demonstrated by laboratory tests. A Human p-tau217 (Phospho Tau 217) Catalogue No.: EH5067 Revision: V4.0 Size: 48T/96T ELISA Kit was used and rang test was (7.813-500pg/ml) which tested by instrument (human reader).
Results: The baseline serum biomarkers analysis of whole Study Participants showed that the mean tau level was 165 ± 84.2 pg/mL, Tau levels increased markedly with disease severity, rising from 86.33 ± 34.40 pg/mL in the control group to 265.72 ± 50.91 pg/mL in the severe group. DSM-5 score also showed a strong positive correlation with Tau concentration, suggesting that higher clinical severity was associated with increased Tau levels. Tau showed very strong negative correlations with ApoE, the correlations' findings indicated that this effect size is substantial up to assay. ApoE demonstrated a mean value of 75.5 ± 55.6 ng/mL. of whole Study Participants. ApoE levels showed a pronounced and significant reduction across disease stages, with the lowest mean value observed in the severe group. While DSM-5 score also showed a negative association with ApoE was strong and significant.
Conclusion: Serum Tau levels increased markedly with disease severity, indicating that Tau may serve as a reliable marker of progressive neuronal injury and neurodegeneration in Alzheimer’s disease. ApoE levels declined substantially with increasing disease severity and showed the highest diagnostic accuracy among the studied biomarkers, indicating its strong potential as a predictive biomarker for Alzheimer’s disease progression.
Ahmed Kadom Kalaf, Khawla A. Shemran, Waleed Azeez AlAmeedy· International Journal of Nut...· 0 citations
Epigenetic changes can affect Alzheimer's disease (AD) susceptibility. miRNAs are novel potential circulating biomarkers of AD and mild cognitive impairment (MCI) that could support cerebrospinal fluid (CSF) biomarkers in earlier diagnosis of the disease or determination of disease stage. Our aim was to assess differences in expression of target miRNAs in patients with different stages of cognitive impairment and to evaluate the association with CSF biomarkers or cognitive test score (MMSE). We included 117 patients with cognitive impairment, among them 62 AD patients, 24 MCI patients with pathological CSF biomarker levels, and 31 MCI patients with normal CSF biomarker levels. Expression of seven target miRNAs was measured in patients' blood plasma, CSF and extracellular vesicles (EVs) enriched from plasma and CSF. None of the investigated miRNAs were differentially expressed between AD and MCI groups. Four miRNAs were associated with CSF biomarker levels, both in plasma (hsa-miR-375-3p) and CSF (hsa-miR-146a-5p, hsa-miR-29c, hsa-miR-107). The observed findings suggest that investigated miRNAs are not suitable for differentiation between different stages of cognitive impairment. However, miRNAs were associated with typical hallmarks of AD, which supports their important role in neurodegeneration. Therefore, miRNA regulatory networks could contribute to better understanding of the biological processes involved in cognitive impairment.
David Vogrinc, M. Holcar, M. Lenassi et al.· Scientific Reports· 0 citations
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.
Xian-Dong Wang, Junchi Wu, Xuan Zhang et al.· Frontiers in Neurology· 0 citations
Background and Objectives Prion diseases can mimic Alzheimer disease (AD) at presentation. Alzheimer's Association AD diagnostic criteria suggest that a single abnormal highly specific plasma biomarker (including p-tau217) is sufficient for a biological diagnosis. We investigated the performance of AD plasma biomarkers in distinguishing AD and prion diseases. Methods We examined plasma biomarker data from patients with prion disease from a prospective cohort study recruited through the UK National Prion Clinic. Prion diseases were diagnosed clinically or with autopsy confirmation, and AD was diagnosed clinically with CSF biomarker confirmation. Plasma p-tau217, p-tau181, Aβ42/40 ratio, brain-derived tau (BD-tau), neurofilament light chain (NfL), and glial fibrillary acid protein (GFAP) were measured using Simoa. Median biomarker values in different groups were compared with Kruskal-Wallis test, and area under the receiver operating characteristic curve was used to compare accuracy in distinguishing prion diseases from sporadic AD (sAD). Lumipulse p-tau217 and NfL were measured in a validation study in a different laboratory. Results In the main study, we analyzed 345 samples from 278 individuals (mean age 58 [SD 13.5], 48.2% female), including 204 with prion diseases (121 sporadic Creutzfeldt-Jakob disease [CJD], 11 iatrogenic CJD, 9 variant CJD, 47 slow-progressing inherited prion disease (IPD) and 16 fast-progressing IPD), 33 with AD, and 41 healthy controls. For discriminating prion disease without AD copathology from sAD, none of p-tau217 (area under the curve [AUC] [95% CI] 0.605 [0.486–0.724]), p-tau181 (AUC 0.554 [0.446–0.661]), or GFAP (AUC 0.514 [0.389–0.640]) performed well. Aβ42/40 discriminated moderately (AUC 0.770 [0.684–0.856]). NfL/p-tau217 ratio (AUC 0.996 [0.987–1.000]), NfL (AUC 0.988 [0.974–1.000]), BD-tau/p-tau217 ratio (AUC 0.963 [0.929–0.996]), and BD-tau (AUC 0.934 [0.890–0.978]) discriminated very well. In an independent validation study, consecutive samples were analyzed from 32 patients with sAD and 35 patients with sporadic Creutzfeldt-Jakob disease (mean age 65.0 [SD 6.4], 56.7% female). NfL/p-tau217 again discriminated almost perfectly (AUC 0.986 [95% CI 0.966–1.000]). Discussion Plasma p-tau217 and p-tau181 are increased in both AD and prion diseases (regardless of burden of AD copathology). Diagnosing AD with a single abnormal p-tau plasma biomarker risks misdiagnosing prion diseases as AD. Plasma NfL/p-tau217 discriminates near-perfectly and could act as a flag to suspect prion diseases where this is a diagnostic possibility. Classification of Evidence This study provides Class II evidence that plasma NfL/p-tau217 discriminates patients with CJD from those with AD.
Thomas Coysh, R. Laban, Elena Veleva et al.· Neurology· 0 citations
Background: Alzheimer’s disease (AD) poses major public health challenges. Traditional CSF and PET diagnostics are invasive, expensive, and limited in routine practice, driving the need for accessible plasma biomarkers.
Objectives: To evaluate the diagnostic and prognostic utility of key plasma biomarkers (plasma Aβ42/Aβ40 ratio, p-tau species, NfL, t-tau, GFAP, sTREM2) and identify limitations to their clinical implementation.
Methods: A structured literature search was conducted in the PubMed database for English-language clinical studies and review articles published between October 2007 and June 2026. Keywords and MeSH terms included "Alzheimer’s disease", "blood-based biomarkers", "immunoprecipitation-mass spectrometry (IP-MS)", and "mild cognitive impairment". Studies focusing on adult clinical biomarkers underwent a narrative synthesis.
Results: Plasma Aβ42/Aβ40 and p-tau species (p-tau181, p-tau231, p-tau217) reliably detect early amyloid pathology and differentiate AD from other dementias. NfL, GFAP, and sTREM2 track axonal damage, astrogliosis, and microglial activity, facilitating disease monitoring and therapeutic response assessment. However, clinical translation is constrained by demographic variations, somatic comorbidities, and a lack of standardized multi-marker reference ranges.
Conclusions: Plasma biomarkers offer a transformative, non-invasive approach to early AD diagnosis and primary care triage, reducing reliance on CSF and PET scans. Overcoming demographic and methodological limitations is essential for their widespread clinical adoption.
Małgorzata Witaszczyk, Alicja Sołtan, Natalia Wiktorzak et al.· International Journal of Inn...· 0 citations
Summary Background Nearly all individuals with Down syndrome (DS) develop Alzheimer’s disease (AD) dementia, primarily due to overexpression of the APP gene. Although specific cerebrospinal fluid (CSF) and plasma tau biomarkers have been investigated in DS-AD, how different tau species change in the DS-AD continuum in comparison to sporadic AD remains uncertain. Methods In this cross-sectional study, we analysed CSF and plasma tau biomarkers in 461 samples from the DABNI and SPIN cohorts, including individuals with DS, cognitively normal euploid participants, and patients with sporadic AD. Biomarker differences were assessed using linear regression with Tukey post hoc comparisons. LOESS modelling was applied to estimate the age at which tau biomarkers became abnormal. Findings We analysed 461 participants from the DABNI and SPIN cohorts. Both CSF and plasma tau biomarkers increased during the asymptomatic stages of DS and in euploid controls, coinciding with Aβ positivity; across the DS clinical spectrum the largest increases were observed for CSF NTA-tau (fold-change [fc] = 6.46–6.94), CSF p-tau217 (fc = 6.43–6.74) and plasma p-tau217 (fc = 4.63–6.54) (linear regression adjusted for age, sex and APOE-ε4 with Tukey post-hoc tests; all p < 0.001). During the dementia stages, CSF tau biomarkers showed only modest further increases (no CSF biomarker differed between pDS and dDS; all p ≥ 0.268), whereas plasma tau biomarkers retained a broader dynamic range across symptomatic phases (pDS vs dDS: plasma p-tau217 p = 0.001, p-tau181 p = 0.002, p-tau231 p = 0.004). Plasma p-tau217 showed the highest diagnostic accuracy, with areas under the curve (AUC) of 0.91–0.97 for biological categorisations and numerically higher values than CSF in symptomatic stages (pDS vs dDS: plasma p-tau217 AUC = 0.69 [95% CI 0.58–0.80] vs CSF p-tau217 AUC = 0.53 [95% CI 0.41–0.65]; DeLong test p = 0.019). In LOESS analyses, tau biomarkers diverged from age-matched controls in the late 30s to early 40s (e.g., plasma p-tau217 ≈ 37.3 years, CSF p-tau181 ≈ 38.1 years) and reached abnormality (+2 SD) over an approximately 20-year span between the fourth and sixth decades, outlining differential but temporally compressed increases. Finally, during symptomatic stages, tau biomarker levels remained stable in DS-AD, in contrast to sporadic AD, where levels declined with advancing age. Interpretation These findings highlight the complementary roles of CSF and plasma tau biomarkers in tracking disease progression: CSF biomarkers capture early pathological changes, whereas plasma biomarkers more effectively reflect disease progression within symptomatic stages. Furthermore, tau biomarkers might support disease staging and monitor clinical progression in DS-AD, but with the need to adapt biomarker frameworks to this specific population. Funding La Caixa Foundation, Instituto de Salud Carlos III, Generalitat de Catalunya, National Institute on Ageing, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, Alzheimer’s Association, National Institute for Health Research, EU Joint Programme–Neurodegenerative Disease Research, Alzheimer’s Society.
J. Arranz, J. Lantero‐Rodriguez, Luisa Sophie Braun-Wohlfahrt et al.· EBioMedicine· 1 citation