Biology subjects

Muniz-Terrera, G.

Publications and source records attributed to Muniz-Terrera, G..

3 recordsLinked to original sources

bioRxiv2024

Impact of cardiometabolic factors and blood beta-amyloid on the volume of white matter hyperintensities in dementia-free subjects with cognitive complaints

IntroductionWhite matter hyperintensities (WMH) in Alzheimers disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid {beta} (A{beta}) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs and cardiometabolic and A{beta} blood biomarkers in a community-based cohort of Latin American CC participants. MethodsWe recruited 112 individuals with CC (69 - 92 YO, 90 females) with available plasma A{beta} biomarkers and cardiometabolic markers (systolic - diastolic blood pressure and glycaemia). WMHs were quantified using a lesion segmentation tool based on SPM12 and segmented using the John Hopkins University (JHU) Atlas and ALVIN segmentation for periventricular and subcortical white matter. Linear multiple regression models were fitted to assess total WMH lesions and the segmented tract, using demographics, cardiometabolic, and A{beta} blood biomarker measures as independent variables. ResultsAfter multiple comparison corrections, diastolic blood pressure was associated with WMHs, specifically in the right anterior thalamic radiation, left cingulum, minor forceps, and subcortical ALVIN segmentation. Glycaemia was associated with WMH volume in forceps major, forceps minor, and right fronto-occipital fasciculi. Conversely, A{beta} blood biomarkers and systolic blood pressure showed no association with WMH overall or in specific tracts. ConclusionOur findings suggest that, in dementia-free CC individuals, WMH volume was more related to cardiometabolic factors, whereas A{beta} blood biomarkers might be of less relevance. Dementia prevention strategies in individuals might be a useful focus for managing high peripheral vessel resistance and endothelial damage due to hypertension and hyperglycaemia.

neuroscience↗

bioRxiv2021

Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936

INTRODUCTIONPlasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimers disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been shown to contribute to synapse degeneration, but it is unknown whether p-tau181 is present in synapses. Here, we tested whether plasma p-tau181predicts cognitive decline and whether it is present in synapses in human brain. METHODSGeneral cognitive ability and plasma p-tau181 concentration were measured in 195 participants at ages 72 and 82. Levels of p-tau181 in total homogenate and synaptic fractions were compared with western blot (n=10-12 per group), and synaptic localisation was examined using array tomography. RESULTSElevated baseline plasma p-tau181 and increasing p-tau181 over time predicted steeper general cognitive decline. We observe p-tau181 in neurites, presynapses, and post-synapses in the brain. DISCUSSIONBaseline and subsequent change in plasma p-tau181 may represent rare biomarkers of differences in cognitive ageing across the 8th decade of life and may play a role in synaptic function in the brain.

neuroscience↗

bioRxiv2020

Variation in VKORC1 is associated with vascular dementia

Genetic variation in VKORC1 is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has also been linked to parental dementia. However, it is unclear whether the relationship persists for the diagnosis in patients themselves, whether the association holds only for certain forms of dementia, and if those taking warfarin are at greater risk. Here, we use data from 211,423 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. We find that the T-allele in rs9923231 confers a greater risk for vascular dementia (OR=1.28, p=0.0069), but not for general dementia (OR=1.04, p=0.21) or Alzheimer dementia (OR=1.05, p=0.35), and that the risk of vascular dementia is not affected by warfarin use in carriers of the T-allele. Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia.

genetics↗