Biology subjects

Alzheimer Disease Neuroimaging Initiative,

Publications and source records attributed to Alzheimer Disease Neuroimaging Initiative,.

5 recordsLinked to original sources

bioRxiv2023

Multimodal Imaging Investigation of Rich Club Alterations in Alzheimer's Disease and Mild Cognitive Impairment: Amyloid Deposition, Structural Atrophy, and Functional Activation Differences

0Alzheimers disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the "rich club," in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach. We employed network analyses of diffusion MRI, longitudinal assessments of gray matter atrophy, amyloid deposition measurements using PET imaging, and meta-analytic data on functional activation differences. Our study focused on evaluating the role of both the core and extended rich club regions in individuals with Mild Cognitive Impairment (MCI) and those diagnosed with Alzheimers Disease. Our findings revealed that rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and Alzheimers Disease. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome.

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bioRxiv2020

Hearing loss in Alzheimer Disease is associated with altered serum lipidomic biomarker profiles

Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.

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bioRxiv2019

Sets of Co-regulated Serum Lipids are Associated with Alzheimer Disease Pathophysiology

INTRODUCTIONAltered regulation of lipid metabolism in Alzheimer disease (AD) can be characterized using lipidomic profiling. METHOD349 serum lipids were measured in 806 participants enrolled in the Alzheimer Disease Neuroimaging Initiative Phase 1 (ADNI1) cohort and analysed using lipid regression models and lipid set enrichment statistics. RESULTSAD diagnosis was associated with 7 of 28 lipid sets of which four also correlated with cognitive decline, including polyunsaturated fatty acids. CSF amyloid beta A{beta}1-42 correlated with glucosylceramides, lysophosphatidyl cholines and unsaturated triacylglycerides; CSF total tau and brain atrophy correlated with monounsaturated sphingomyelins and ceramides, in addition to EPA-containing lipids. DISCUSSIONLipid desaturation, elongation and acyl chain remodeling are dysregulated across the spectrum of AD pathogenesis. Monounsaturated lipids were important in early stages of AD, while polyunsaturated lipid metabolism was associated with later stages of AD. SIGNFICANCEBoth metabolic genes and co-morbidity with metabolic diseases indicate that lipid metabolism is critical in the etiology of Alzheimers disease (AD). For 800 subjects, we found that sets of blood lipids were associated with current AD-biomarkers and with AD clinical symptoms. Our study highlights the role of disturbed acyl chain lipid remodelling in several lipid classes. Our work has significant implications on finding a cure for AD. Depending on subject age, human blood lipids may have different effects on AD development. Remodelling of acyl chains needs to be studied in relation to genetic variants and environmental factors. Specifically, the impact of dietary supplements and drugs on lipid remodelling must be investigated.

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bioRxiv2019

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer disease and three causality networks of AD: the GR@ACE project.

BackgroundGenetics plays a major role in Alzheimers Disease (AD). To date, 40 genes associated with AD have been identified, although most remain undiscovered. Clinical, neuropathological and genetic variability might impact genetic discoveries and complicate dissection of the biological pathways underlying AD. MethodsGR@ACE is a genome-wide study of dementia and its clinical endophenotypes that encompasses 4,120 cases and 3,289 controls from Spain. GR@ACE phenotypes were defined according to ADs clinical certainty and the presence of vascular co-morbidity. To explore whether clinical endophenotypes reflect variation in underlying biological pathways, we first assessed the impact of known AD loci across endophenotypes to generate three loci categories. Next, we incorporated gene co-expression data and conducted pathway analysis on each category. To assess the impact of heterogeneity in the GWAS findings, the GR@ACE series were meta-analyzed with: 1) genotype-level data from dbGaP (N=21,235); and 2) summary statistics from IGAP Stages I and II (n=61,571 and n=81,455 respectively). FindingsWe classified known AD loci in three categories, which might reflect the disease clinical heterogeneity, from vascular and mixed forms to pure AD pathology. Immune system pathways were detected in all categories. Intriguingly, vascular processes were only detected as a causal mechanism in probable AD. A meta-analysis of GR@ACE with additional GWAS datasets revealed the ANKRD31-rs4704171 signal in the HMGCR genomic region. We confirmed NDUFAF6-rs10098778 and SCIMP-rs7225151, which were previously detected by IGAP, to be suggestive signals. We also confirmed CD33-rs3865444 to be genome-wide significant. InterpretationThe regulation of vasculature is a prominent causal component of probable AD. In that context, cerebral amyloid angiopathy, the unique identified link between the vascular and amyloid hypotheses, deserves further investigation. The GR@ACE meta-analysis revealed novel AD genetic signals. GWAS results are strongly driven by the presence of clinical heterogeneity in the AD series. FundingGrifols SA, Fundacion bancaria "La Caixa", Fundacio ACE and ISCIII (Instituto de Salud Carlos III).

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bioRxiv2018

Causal influences of brain metabolic activity reveal interregional progressions in normal aging

During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and LASSO (least absolute shrinkage and selection operator) regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG-PET). We analyzed FDG-PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of about one year. The longitudinal data were concatenated across subjects to form a time series, and the first order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.

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