Search

Background Two of the main causes for dementia are Alzheimer's disease (AD) and vascular pathology, with most patients showing mixed pathology. Plasma biomarkers for Alzheimer's disease‐related pathology have recently emerged, including Aβ (amyloid‐beta), p‐tau (phosphorylated tau), NfL (neurofilament light), and GFAP (glial fibrillary acidic protein). There is a current gap in the literature regarding whether there is an association between these plasma biomarkers with vascular pathology and neurodegeneration. Methods and Results Cross‐sectional data from 594 individuals (mean [SD] age: 64 [8] years; 17% female) were included from the SMART‐MR (Second Manifestations of Arterial Disease‐Magnetic Resonance) study, a prospective cohort study of individuals with a history of arterial disease. Plasma markers were assessed using single molecular array assays (Quanterix). Magnetic resonance imaging markers included white matter hyperintensity volume, presence of infarcts (yes/no), total brain volume, and hippocampal volume assessed on 1.5T magnetic resonance imaging. Linear regressions were performed for each standardized plasma marker with white matter hyperintensity volume, total brain volume, and hippocampal volume as separate outcomes, correcting for age, sex, education, and intracranial volume. Logistic regressions were performed for the presence of lacunar and cortical infarcts. Higher p‐tau181 was associated with larger white matter hyperintensity volume (b per SD increase=0.16 [95% CI, 0.06–0.26], P=0.015). Higher NfL (b=−5.63, [95% CI, −8.95 to −2.31], P=0.015) was associated with lower total brain volume and the presence of infarcts (odds ratio [OR], 1.42 [95% CI, 1.13–1.78], P=0.039). Higher GFAP levels were associated with cortical infarcts (OR, 1.45 [95% CI, 1.09–1.92], P=0.010). Conclusions Plasma biomarkers that have been associated with tau pathology, axonal injury, and astrocytic activation are related to magnetic resonance imagingmarkers of vascular pathology and neurodegeneration in patients with manifest arterial disease.

Abstract Introduction This study investigates whether plasma biomarkers (Aβ42/40 and p‐tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo. Methods Forty‐four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aβ42, Aβ40, Aβ42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status. Results Patients with pAD had significantly lower plasma Aβ42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aβ40, Aβ42, or P‐tau 181. Results showed that Aβ42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P‐tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68–0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66–0.86) and APOE E4 (AUC = 0.69 (CI 0.57–0.81) in discriminating pAD from HC. Discussion These results demonstrate associations between select plasma biomarker of AD pathology (Aβ42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings.

Abstract Interpretation of axonal damage biomarker Neurofilament Light chain (NfL) concentrations is difficult due to the lack of age‐specific and disease‐specific reference values. We here developed an interactive interface to support interpretation of NfL results in human body fluids. We used NfL values of 1698 individuals without a neurological disorder, aged 19–85 years, and patients with MS and dementias. Percentile regression estimates per diagnosis populate interactive graphs, alongside NfL background information (available on: https://mybiomarkers.shinyapps.io/Neurofilament). This accessible interface provides reference for interpretation of the individual patient results for clinicians. It showcases an adaptable method to support interpretation of age‐dependent biomarkers in neurology.

Abstract Introduction Blood‐based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)–based assays currently used in clinical settings. In this study, we examined different blood‐based assays to measure Aβ and how they compare among centers and assays. Methods Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass‐spectrometric methods were used to measure plasma Aβ concentrations. Results Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre‐analytical sample handling and specificity, and cross‐reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study.