Background It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected... Show moreBackground It has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected individual. These findings have generated the concept of using seropositivity for antibodies against M. leprae PGL-I as an indicator of the proportion of the population that has been infected. Although anti-PGL-I IgM levels provide information on whether an individual has ever been infected, their presence cannot discriminate between recent and past infections. Since infection in (young) children by definition indicates recent transmission, we piloted the feasibility of assessment of anti-PGL-I IgM seroprevalence among children in a leprosy endemic area in India as a proxy for recent M. leprae transmission.Material and methods A serosurvey for anti-PGL-I IgM antibodies among children in highly leprosy endemic villages in Bihar, India, was performed, applying the quantitative anti-PGL-I UCP-LFA cassette combined with low-invasive, small-volume fingerstick blood (FSB).Results Local staff obtained FSB of 1,857 children (age 3-11 years) living in 12 leprosy endemic villages in Bihar; of these, 215 children (11.58%) were seropositive for anti-PGL-I IgM.Conclusion The anti-PGL-I seroprevalence level of 11.58% among children corresponds with the seroprevalence levels described in studies in other leprosy endemic areas over the past decades where no prophylactic interventions have taken place. The anti-PGL-I UCP-LFA was found to be a low-complexity tool that could be practically combined with serosurveys and was well-accepted by both healthcare staff and the population. On route to leprosy elimination, quantitative anti-PGL-I serology in young children holds promise as a strategy to monitor recent M. leprae transmission in an area. Show less
Chatterjee, P.; Tegg, M.; Pedrini, S.; Fagan, A.M.; Xiong, C.J.; Singh, A.K.; ... ; Dominantly Inherited Alzheimer Net 2021
Plasma amyloid-beta (A beta) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be... Show morePlasma amyloid-beta (A beta) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma A beta alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two A beta measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3-4 years later (NC = 8; MC = 9). Plasma A beta 1-40 and A beta 1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(A beta 1-40: p = 0.001; A beta 1-42: p = 0.0004) and T2 (A beta 1-40: p = 0.001; A beta 1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma A beta 1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma A beta 1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma A beta may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required. Show less
Chatterjee, P.; Fagan, A.M.; Xiong, C.J.; McKay, M.; Bhatnagar, A.; Wu, Y.Q.; ... ; Dominantly Inherited Alzheimer Net 2021
Objective: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs).Methods: Plasma metabolites were measured using mass... Show moreObjective: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs).Methods: Plasma metabolites were measured using mass-spectrometry (AbsoluteIDQ (R) p400 HR kit) and were compared between pre-symptomatic D-CAA MCs (n= 9) and non-carriers (D-CAA NCs, n= 8) from the same pedigree. Metabolites that survived correction for multiple comparisons were further compared between D-CAA MCs and additional control groups (cognitively unimpaired adults).Results: 275 metabolites were measured in the plasma, 22 of which were observed to be significantly lower in the D-CAA MCs compared to D-CAA NCs, following adjustment for potential confounding factors age, sex, and APOE epsilon 4 (p < 00.05). After adjusting for multiple comparisons, only spermidine remained significantly lower in the D-CAA MCs compared to the D-CAA NCs (p < 0.00018). Plasma spermidine was also significantly lower in D-CAA MCs compared to the cognitively unimpaired young adult and older adult groups (p < 0.01). Spermidine was also observed to correlate with CSF A beta(40) (r(s) = 0.621, p = 0.024), CSF A beta(42) (r(s) = 0.714, p = 0.006), and brain A beta load (r(s) = -0.527, p = 0.030).Conclusion: The current study provides pilot data on D-CAA linked metabolite signals, that also associated with A beta neuropathology and are involved in several biological pathways that have previously been linked to neurodegeneration and dementia. Show less
