Biology subjects

Alzheimer's Disease Neuroimaging Initiative (ADNI),

Publications and source records attributed to Alzheimer's Disease Neuroimaging Initiative (ADNI),.

4 recordsLinked to original sources

bioRxiv2022

FMRI complexity correlates with tau-PET in Late-Onset and Autosomal Dominant Alzheimer's Disease

Neurofibrillary tangle pathology detected with tau-PET correlates closely with neuronal injury and cognitive symptoms in Alzheimers disease (AD). Complexity of rs-fMRI time-series, measured by entropy values, have recently been reported to decrease with aging, APOE {varepsilon}4 genotype and cognitive decline in AD. Here we hypothesize that the complexity of BOLD signals provides an index for tau-related neuronal injury and cognitive decline in the AD process. Data were obtained from the Alzheimers Disease Neuroimaging Initiative phase 3 (ADNI3) and the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) study, including cognitively normal elderly controls, persons with late onset AD (LOAD) and early onset autosomal dominant AD (ADAD) patients and their relatives. Our cohort consisted of a sample of 147 subjects from ADNI3 and 41 subjects from EEAJ with T1 structural, tau-PET (tracer: 18F-AV1451) and fMRI scans. Correlations between SUVR tau-PET and multi-scale entropy (MSE) were calculated voxelwise as well as for standard automated anatomical labeling (AAL) atlas regions while accounting for age, gender, and regional gray matter volume. Potential pathways relating MSE to cognitive function mediated through tau-PET were assessed by path analysis. We found significant negative correlations between low frequency MSE and tau-PET measures in medial temporal lobe, in both ADNI3 and EEAJ cohorts. Furthermore, low frequency MSE showed significant associations with the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Status Exam (MMSE) scores in both ADNI3 and EEAJ cohorts, which were largely mediated through the tau-PET signal. Correlations of MSE with tau-PET in temporal lobes support our hypothesis that the complexity of rs-fMRI is associated with regional tau protein accumulation. Furthermore, the association of MSE with CDR and MMSE, mediated by tau-PET, in disease relevant areas suggests that a reduction in MSE is indicative of decreased information processing capacity and cognitive decline in AD processes.

neuroscience↗

bioRxiv2020

Functional brain age prediction suggests accelerated aging in preclinical familial Alzheimer's disease, irrespective of fibrillar amyloid-beta pathology

We aimed at developing a model able to predict brain aging from resting state functional connectivity (rs-fMRI) and assessing whether genetic risk/determinants of Alzheimers disease (AD) and amyloid (A{beta}) pathology contributes to accelerated brain aging. Using data collected in 1340 cognitively unimpaired participants from 18 to 94 years old selected across multi-site cohorts, we showed that chronological age can be predicted across the whole lifespan from topological properties of graphs constructed from rs-fMRI. We subsequently used the difference between the model-predicted age and the chronological age in pre-symptomatic autosomal dominant AD (ADAD) mutation carriers and asymptomatic individuals at risk of sporadic AD and assessed the influence of genetics and A{beta} pathology on brain age. Applying our predictive model in the context of preclinical AD revealed that the pre-symptomatic phase of ADAD is characterized by accelerated functional brain aging. This phenomenon is independent from, and might precede, detectable fibrillar A{beta} deposition.

neuroscience↗

bioRxiv2019

Genome-wide association study of Alzheimer’s disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset

Alzheimers disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimers Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures of amyloid-beta (A{beta}) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to A{beta}42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-A{beta}38 and CSF-A{beta}40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-A{beta} and -tau related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.

genomics↗

bioRxiv2018

Altered BOLD signal variation in Alzheimer’s disease and frontotemporal dementia

Recently discovered glymphatic brain clearance mechanisms utilizing physiological pulsations have been shown to fail at removing waste materials such as amyloid and tau plaques in neurodegenerative diseases. Since cardiovascular pulsations are a main driving force of the clearance, this research investigates if commonly available blood oxygen level-dependent (BOLD) signals at 1.5 and 3 T could detect abnormal physiological pulsations in neurodegenerative diseases. Coefficient of variation in BOLD signal (CVBOLD) was used to estimate contribution of physiological signals in Alzheimers disease (AD) and behavioural variant frontotemporal dementia (bvFTD). 17 AD patients and 18 bvFTD patients were compared to 24 control subjects imaged with a 1.5 T setup from a local institute. AD results were further verified with 3 T data from the Alzheimers disease neuroimaging initiative (ADNI) repository with 30 AD patients and 40 matched controls. Effect of motion and gray matter atrophy was evaluated and receiver operating characteristic (ROC) analyses was performed.\n\nThe CVBOLD was higher in both AD and bvFTD groups compared to controls (p < 0.0005). The difference was not explained by head motion or gray matter atrophy. In AD patients, the CVBOLD alterations were localized in overlapping structures in both 1.5 T and 3 T data. Localization of the CVBOLD alterations was different in AD than in bvFTD. Areas where CVBOLD is higher in patient groups than in control group involved periventricular white matter, basal ganglia and multiple cortical structures. Notably, a robust difference between AD and bvFTD groups was found in the CVBOLD of frontal poles. In the analysis of diagnostic accuracy, the CVBOLD metrics area under the ROC for detecting disease ranged 0.85 - 0.96.\n\nConclusionsThe analysis of brain physiological pulsations measured using CVBOLD reveals disease-specific alterations in both AD and bvFTD.

neuroscience↗