Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 5, 2024

Abstract Our current understanding of the spread and neurodegenerative effects tau neurofibrillary tangles (NFTs) within medial temporal lobe (MTL) during early stages Alzheimer’s Disease (AD) is limited by presence confounding non-AD pathologies two-dimensional (2-D) nature conventional histology studies. Here, we combine ex vivo MRI serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization quantitative NFT burden measures in space high-resolution, atlas with cytoarchitecturally-defined subregion labels, that can be used inform future neuroimaging Average maps show clear anterior poster gradient distribution precise, spatial pattern highest levels NFTs found not just transentorhinal region but also cornu ammonis (CA1) subfield. Additionally, identify granular regions where neurodegeneration are likely linked specifically, thus potentially more sensitive as AD biomarkers.

Язык: Английский

---

Anterior-temporal network hyperconnectivity is key to Alzheimer's disease: from ageing to dementia

Brain, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract Curing Alzheimer’s disease remains hampered by an incomplete understanding of its pathophysiology and progression. Exploring dysfunction in medial temporal lobe networks, particularly the anterior-temporal (AT) posterior-medial (PM) systems, may provide key insights, as these networks exhibit functional connectivity alterations along entire continuum, potentially influencing propagation. However, specific changes each network their clinical relevance across stages are not yet fully understood. This requires considering commonly used biomarkers, progression, individual variability, age confounds. Here, we leveraged monocentric longitudinal data from 261 participants spanning adult lifespan continuum. The sample included cognitively unimpaired adults aged 19 to 85 years (n = 209; eight out 64 older over 60 were Aβ-positive) Aβ-positive patients fulfilling diagnostic criteria for mild cognitive impairment (MCI, n 26; 18 progressed Alzheimer-dementia within seven years) or type dementia 26). Participants underwent structural resting-state (f) MRI, florbetapir FDG-PET, global assessments, with up three visits a maximum period 47 months. Network was assessed using seed-based analyses perirhinal parahippocampal cortices seeds, data-driven masks reflecting AT PM networks. Generalized additive linear mixed models run assess age-specific effects Alzheimer’s-related alterations. In this context, explored various markers pathological severity, including cerebral amyloid uptake, glucose metabolism, hippocampal volume, cognition, staging, time onset. Our findings revealed distinct patterns linked normal aging disease. Advancing throughout adulthood associated lower more subtle connectivity, while characterised hyperconnectivity without connectivity. Specifically, higher MCI compared controls positively burden, hypometabolism, atrophy, deficits adults, ranging demented. Additionally, correlated faster progression patients. comprehensive approach allowed reveal that excessive is intrinsically These insights guide future research better understand cascading events leading hold promise developing prognostic tools therapeutic interventions targeting

Язык: Английский

---

Brain age prediction using the graph neural network based on resting-state functional MRI in Alzheimer's disease

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 30, 2023

Introduction Alzheimer's disease (AD) is a neurodegenerative that significantly impacts the quality of life patients and their families. Neuroimaging-driven brain age prediction has been proposed as potential biomarker to detect mental disorders, such AD, aiding in studying its effects on functional networks. Previous studies have shown individuals with AD display impaired resting-state connections. However, most used structural magnetic resonance imaging (MRI), limited based MRI (rs-fMRI). Methods In this study, we applied graph neural network (GNN) model controls predict ages using rs-fMRI AD. We compared performance GNN traditional machine learning models. Finally, post hoc was also identify critical regions Results The experimental results demonstrate our can normal data from ADNI database. Moreover differences between chronological were more significant than controls. Our suggest associated accelerated aging connectivity an effective tool for predicting age. Discussion study provides evidence promising modality research, proves be Furthermore, hippocampus, parahippocampal gyrus, amygdala are verified.

Язык: Английский

---

Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum

Acta Neuropathologica, Год журнала: 2024, Номер 148(1)

Опубликована: Сен. 3, 2024

Язык: Английский

---

BOLD Amplitude Correlates of Preclinical Alzheimer’s Disease

Neurobiology of Aging, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

Differential effects of aging, Alzheimer's pathology, and APOE4 on longitudinal functional connectivity and episodic memory in older adults

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 25, 2025

Abstract Background Both aging and Alzheimer's disease (AD) affect brain networks, with early disruptions occurring in regions involved episodic memory. Few studies have, however, focused on distinguishing region-specific effects of AD-biomarker negative “normal” amyloid- tau pathology functional connectivity. Further, longitudinal combining imaging, biomarkers, cognition are rare. Methods We assessed resting-state connectivity (rsFC) strength graph measures the memory network including medial temporal lobe (MTL), posteromedial cortex (PMC), prefrontal alongside over two years. For this preregistered study, we included 100 older adults who were tau-negative using CSF PET measurements to investigate aging, 70 had data available changes related AD pathology. All participants cognitively unimpaired from PREVENT-AD cohort. used region interest (ROI)-to-ROI bivariate correlations, analysis, multiple regression models. Results In sample, rsFC within PMC, between parahippocampal inferomedial precuneus, posterior hippocampus precuneus decreased time. Additionally, observed a decrease global efficiency. there was steeper efficiency higher baseline age particularly parahippocampal-gyrus regions. lower PMC associated poorer performance. sample data, increase anterior superior Higher MTL-PMC differentially trajectories depending APOE4 genotype. Conclusions Our findings suggest differential Hypoconnectivity cognitive decline. hyperconnectivity decline carriers. Future should more diverse samples, nonetheless, our approach allowed us identify pathology, enhancing cross-sectional research. Hyperconnectivity has been proposed as mechanism before, now contribute specific connections focus future Graphical A ) “Normal aging” tau- biomarker status characterized by strength. B Cognitively Alzheimer’s at (measured via cerebrospinal fluid) exhibited

Язык: Английский

---

Object fine-grained discrimination as a sensitive cognitive marker of transentorhinal integrity

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Май 25, 2025

The transentorhinal cortex (tErC) is one of the first regions affected by Alzheimer's disease (AD), often showing changes before clinical symptoms appear. Understanding its role in cognition key to detecting early cognitive impairments AD. This study tested hypothesis that tErC supports fine-grained representations unique individual objects, sensitively granularity demanded discrimination, influencing both perceptual and mnemonic functions. We examined tErC's object versus scene using objective (based on a pretrained convolutional neural network, CNN) subjective (human-rated) measures visual similarity. Our results show structural integrity specifically related sensitivity similarity for but not scenes. Importantly, this relationship depends how measured: it appears only when CNN solely ratings discrimination. Furthermore, was associated with tErC-BA36 connectivity, computed from ratings. Altogether, these findings suggest discrimination may represent specific marker after accounting type measured.

Язык: Английский

---

A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Апрель 24, 2024

To investigate the abnormalities of three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Язык: Английский

---

Exploring intricate connectivity patterns for cognitive functioning and neurological disorders: incorporating frequency-domain NC method into fMRI analysis

Cerebral Cortex, Год журнала: 2024, Номер 34(5)

Опубликована: Май 1, 2024

Abstract This study extends the application of frequency-domain new causality method to functional magnetic resonance imaging analysis. Strong causality, weak balanced cyclic and transitivity were constructed simulate varying degrees causal associations among multivariate functional-magnetic-resonance-imaging blood-oxygen-level-dependent signals. Data from 1,252 groups individuals with different cognitive impairment collected. The was employed construct directed efficient connectivity networks brain, analyze statistical characteristics topological variations in brain regions related impairment, utilize these as features for training a deep learning model. results demonstrated that accurately detected simulated signals degrees. tests also confirmed superior performance surpassing other three methods terms accuracy, precision, recall rates. Furthermore, consistent significant differences observed efficiency networks, where several subregions defined by multimodal parcellation Human Connectome Project simultaneously appeared patient groups. suggests association between fine-grained cortical subregions, driven data segmentation, human function, making them potential biomarkers further analysis Alzheimer’s disease.

Язык: Английский

---

Pathological and neurochemical correlates of locus coeruleus functional network activity

Biological Psychology, Год журнала: 2024, Номер 192, С. 108847 - 108847

Опубликована: Июль 20, 2024

The locus coeruleus (LC) produces the neuromodulators norepinephrine and dopamine, projects widely to subcortical cortical brain regions. LC has been a focus of neuroimaging biomarker development for early detection Alzheimer's disease (AD) since it was identified as one earliest regions develop tau pathology. Our recent research established use positron emission tomography (PET) measure catecholamine synthesis capacity in cognitively unimpaired older adults. We extend this work by investigating possible influence pathology neurochemical function on network activity using functional magnetic resonance imaging (fMRI). In separate sessions, participants underwent PET ([18F]Fluoro-m-tyrosine), ([18F]Flortaucipir), amyloid-β ([11C]Pittsburgh compound B), fMRI at rest. Consistent with growing body aging preclinical AD, we find that higher is associated burden individuals risk developing AD (amyloid-β positive). Critically, relationships between tau) were moderated capacity. High levels reduced Broadly, these findings support view individual differences are shaped interactions neuromodulator function, point systems potential therapeutic targets.

Язык: Английский

---