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Biomedical subjects

Brian Lawlor

Publications and source records attributed to Brian Lawlor.

2 recordsLinked to original sources

Blood-based biomarkers of Alzheimer's disease and neurodegeneration in an indigenous African cohort using both Simoa and NULISA platforms.

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&#x2009;=&#x2009;967) underwent biomarker quantification in plasma (p-tau217, GFAP, NfL, A&#x3b2;42 and A&#x3b2;40) 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&#x2009;<&#x2009;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.

Biomarkers

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P &#x2264; 1 &#xd7; 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 &#xd7; 10(-17); including ADGC data, meta P = 5.0 &#xd7; 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 &#xd7; 10(-14); including ADGC data, meta P = 1.2 &#xd7; 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 &#xd7; 10(-4); including ADGC data, meta P = 8.6 &#xd7; 10(-9)), CD33 (GERAD+, P = 2.2 &#xd7; 10(-4); including ADGC data, meta P = 1.6 &#xd7; 10(-9)) and EPHA1 (GERAD+, P = 3.4 &#xd7; 10(-4); including ADGC data, meta P = 6.0 &#xd7; 10(-10)).

ATP-Binding Cassette Transporters