Biology subjects

Kocagoncu, E.

Publications and source records attributed to Kocagoncu, E..

4 recordsLinked to original sources

bioRxiv2026

NTAD: A longitudinal neuroimaging dataset of Alzheimer's disease pathology

We introduce the New Therapeutics in Alzheimer's Disease (NTAD) dataset, a multi-modal and longitudinal imaging dataset from 70 biomarker-positive people with early dementia or Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD), assessed over 2.5 years, and 35 healthy controls assessed at baseline. The data include simultaneous magneto- and electro-encephalography (M/EEG), 3-Tesla structural and functional magnetic resonance imaging (MRI), Amyloid-beta; positron emission tomography (PET), fluid proteomic biomarkers in cerebrospinal fluid and blood, and a battery of clinical and neuropsychological assessments. 11C UCB-J PET was undertaken for a subset of participants. For people with AD, assessments were repeated at approximately three weeks, 15 months, and 28 months after baseline. The data can be accessed through the Dementias Platform UK (DPUK), including pre-processed M/EEG and T1 MRI in pseudonymised BIDS format. With the pressing need to develop treatments for slowing, reversing, and preventing AD, these data provide an opportunity for identifying and validating novel biomarkers of Alzheimer's disease neurophysiology, as well as understanding its treatable pathology.

neuroscience↗

bioRxiv2023

iPSC-Astrocyte morphology reflects patient clinical markers

Human iPSCs provide powerful cellular models of Alzheimers disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimers disease (AD) reflect clinical markers, including {beta}-amyloid (A{beta}) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets. In this work iPSC-derived astrocytes were generated from a cohort of individuals with high versus low levels of the inflammatory marker YKL-40, in their cerebrospinal fluid (CSF). iPSC-derived astrocytes were treated with exogenous A{beta} oligomers and high content imaging demonstrated a correlation between astrocytes that underwent the greatest morphology change from patients with low levels of CSF-YKL-40 and more protective APOE genotypes. This finding was subsequently verified using similarity learning as an unbiased approach. This study shows that iPSC-derived astrocytes from AD patients reflect key aspects of the pathophysiological phenotype of those same patients, thereby offering a novel means of modelling AD, stratifying AD patients and conducting therapeutic screens. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/548687v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1df3486org.highwire.dtl.DTLVardef@f184d8org.highwire.dtl.DTLVardef@48a33dorg.highwire.dtl.DTLVardef@d53a90_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Neurons derived from individual early Alzheimer's disease patients reflect clinical vulnerability

Establishing preclinical models of Alzheimers disease that predict clinical outcomes remains a critically important, yet to date not fully realised, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences that are apparent in patients. Here we report an approach using induced pluripotent stem cell-derived cortical neurons from people with early symptomatic Alzheimers disease where we sought a match between individual disease characteristics in cells with analogous characteristics in the people from whom they were derived. We show that the response to amyloid-{beta} burden in life, as measured by cognitive decline and brain activity levels, varies between individuals and this vulnerability rating correlates with the individual cellular vulnerability to extrinsic amyloid-{beta} in vitro as measured by synapse loss and function. Our findings indicate that patient induced pluripotent stem cell-derived cortical neurons not only present key aspects of Alzheimers disease pathology, but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individuals in-life clinical vulnerability thus represent a tractable method of Alzheimers disease modelling using clinical data in combination with cellular phenotypes.

neuroscience↗

bioRxiv2019

Tau pathology in early Alzheimer’s disease disrupts selective neurophysiological networks dynamics

The role of aggregation of misfolded Tau protein in the pathogenesis of Alzheimers disease is the subject of rapid biomarker development and new therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography (E/MEG) in combination with [18F]AV1451 PET scanning to quantify Tau-dependent network disruption. Using a graph theoretical approach to MEG connectivity, we quantified nodal measures of functional segregation, centrality and efficiency of information transfer. We correlated these metrics against the nodes uptake of [18F]AV1451. There were both regional- and frequency-specific effects of Tau levels on the efficiency of information transfer and network segregation in early AD. Tau correlated with temporal regional participation coefficient (in delta, theta, beta bands); and temporal lobar eigenvector centrality (in theta, alpha, beta bands), but greater eccentricity at higher frequencies (gamma). The results support the translational development of neurophysiological "signatures" as biomarkers of Alzheimers disease, with potential to facilitate experimental medicines studies.

neuroscience↗