Tau-PET pathology in the subregions of the amygdala and its associations with cognitive performance and neuropsychiatric symptoms in autosomal dominant Alzheimer’s disease DOI Creative Commons
Catarina Tristão‐Pereira, Stephanie Langella, Justin S. Sanchez

и другие.

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

Опубликована: Март 20, 2025

The amygdala plays a role in behavior and emotional response is vulnerable to Alzheimer's disease (AD) pathology, yet little known about tau accumulation before clinical symptom onset. To investigate whether certain nuclei are particularly degeneration might underlie early neuropsychiatric symptoms AD, we aimed characterize subregional pathology its correlates associations with established biomarkers of AD cognitive-behavioral measures Presenilin-1 E280A mutation carriers autosomal dominant AD. Participants included 25 cognitively unimpaired 37 non-carrier family members from the Colombia-Boston (COLBOS) Biomarker Study. Measures 18F-flortaucipir, 11C-Pittsburgh compound B, Consortium Establish Registry for Disease Word List Learning, Trail Making Test, Geriatric Depression Scale, Anxiety Inventory. We examined group differences levels (whole amygdala, lateral nucleus basal nucleus) analyzed markers measures. Amygdala were higher compared non-carriers. Among carriers, showed greater burden than nucleus, correlated closer estimated age onset increased cortical amyloid. Additionally, both was associated poorer working memory, lower executive function depressive symptoms. However, did not correlate anxiety. Notably, differentiated non-carriers, predictive accuracy when included. These findings suggest that begins while cognitive deficits nuclei's differential vulnerability underscores importance investigating spread within amygdala-associated networks, relative manifestations This study reinforces potential as valuable biomarker preclinical

Язык: Английский

Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases DOI
Martin Kampmann

Nature reviews. Neuroscience, Год журнала: 2024, Номер 25(5), С. 351 - 371

Опубликована: Апрель 4, 2024

Язык: Английский

Процитировано

34
Virtual brain twins: from basic neuroscience to clinical use DOI Creative Commons
Huifang Wang, Paul Triebkorn, Martin Breyton

и другие.

National Science Review, Год журнала: 2024, Номер 11(5)

Опубликована: Фев. 27, 2024

ABSTRACT Virtual brain twins are personalized, generative and adaptive models based on data from an individual’s for scientific clinical use. After a description of the key elements virtual twins, we present standard model personalized whole-brain network models. The personalization is accomplished using subject’s imaging by three means: (1) assemble cortical subcortical areas in subject-specific space; (2) directly map connectivity into models, which can be generalized to other parameters; (3) estimate relevant parameters through inversion, typically probabilistic machine learning. We use healthy ageing five diseases: epilepsy, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease psychiatric disorders. Specifically, introduce spatial masks demonstrate their physiological pathophysiological hypotheses. Finally, pinpoint challenges future directions.

Язык: Английский

Процитировано

24
Glioblastoma and brain connectivity: the need for a paradigm shift DOI
Alessandro Salvalaggio,

Lorenzo Pini,

Alessandra Bertoldo

и другие.

The Lancet Neurology, Год журнала: 2024, Номер 23(7), С. 740 - 748

Опубликована: Июнь 13, 2024

Язык: Английский

Процитировано

16
Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer’s disease DOI Open Access
Sebastian Niclas Roemer,

Franziska Wagner,

Lisa Evangelista

и другие.

Science Translational Medicine, Год журнала: 2025, Номер 17(782)

Опубликована: Янв. 22, 2025

In Alzheimer’s disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration cognitive decline. However, pathophysiological link between Aβ remains unclear, hinders therapeutic efforts to attenuate Aβ-related accumulation. has been found trigger neuronal hyperactivity hyperconnectivity, preclinical research shown that spreads across connected neurons in an activity-dependent manner. Here, we hypothesized hypersynchronicity, resulting functional connectivity increases, constitute a crucial mechanism by facilitates pathology. By combining positron emission tomography (PET), resting-state magnetic resonance imaging, longitudinal tau-PET 69 cognitively normal amyloid-negative controls 140 amyloid-positive patients covering AD spectrum, confirmed induces hyperconnectivity temporal lobe epicenters posterior brain regions are vulnerable accumulation AD. This was replicated independent sample 55 345 individuals with low cortical uptake, suggesting emergence precedes neocortical . Last, using mediation analysis, these increases typical tau-vulnerable mediated effect on faster accumulation, unveiling increased as potential causal two hallmark pathologies. Together, findings suggest promotes eliciting targeting may

Язык: Английский

Процитировано

4
Astrocytes in selective vulnerability to neurodegenerative disease DOI Creative Commons
Till S. Zimmer, Adam L. Orr, Anna G. Orr

и другие.

Trends in Neurosciences, Год журнала: 2024, Номер 47(4), С. 289 - 302

Опубликована: Март 22, 2024

Selective vulnerability of specific brain regions and cell populations is a hallmark neurodegenerative disorders. Mechanisms selective involve neuronal heterogeneity, functional specializations, differential sensitivities to stressors pathogenic factors. In this review we discuss the growing body literature suggesting that, like neurons, astrocytes are heterogeneous specialized, respond integrate diverse inputs, induce effects on function. disease, undergo specific, context-dependent changes that promote different trajectories outcomes. We propose contribute through maladaptive transitions context-divergent phenotypes impair functions. Further studies multifaceted roles in disease may provide new therapeutic approaches enhance resilience against

Язык: Английский

Процитировано

14
Amidst an amygdala renaissance in Alzheimer’s disease DOI Creative Commons
Kaitlin Stouffer, Xenia Grande, Emrah Düzel

и другие.

Brain, Год журнала: 2023, Номер 147(3), С. 816 - 829

Опубликована: Дек. 18, 2023

Abstract The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer’s disease the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances imaging image analysis techniques. Here, we provide a cross-disciplinary overview of neuroimaging studies on amygdala. These strong support role utility biomarkers detecting changes predicting decline cognitive functions neuropsychiatric symptoms stages. We summarize animal literature connectivity amygdala, demonstrating that nuclei show earliest strongest accumulation are those connected to brain regions also accumulation. Additionally, propose alternative pathway spreading within medial temporal lobe between anterior hippocampus. proposed existence this is strengthened novel experimental data human functional connectivity. Finally, roles highlighting correspondence symptomatic profiles disease. In summary, these findings new impetus studying unique perspective guide further study occurrence

Язык: Английский

Процитировано

20
Associations of quantitative susceptibility mapping with cortical atrophy and brain connectome in Alzheimer's disease: A multi-parametric study DOI Creative Commons
Haojie Chen, Aocai Yang, Weijie Huang

и другие.

NeuroImage, Год журнала: 2024, Номер 290, С. 120555 - 120555

Опубликована: Март 5, 2024

Aberrant susceptibility due to iron level abnormality and brain network disconnections are observed in Alzheimer's disease (AD), with disrupted homeostasis hypothesized be linked AD pathology neuronal loss. However, whether associations exist between abnormal quantitative mapping (QSM), atrophy, altered connectome remains unclear. Based on multi-parametric imaging data from 30 patients 26 healthy controls enrolled at the China-Japan Friendship Hospital, we investigated of QSM signal volumetric measure across 246 regions patients. The structural functional connectomes were constructed based diffusion MRI tractography connectivity, respectively. topology was quantified using graph theory analyses. We revealed seven both reduced cortical thickness (p<0.05) AD, including right superior frontal gyrus, left temporal fusiform parietal lobule, inferior precuneus. Correlations computed subjects specific group resulted statistically significant correlations five these regions, higher compared topology. correlation topological metrics, value individual group-averaged levels, resulting a call spatial correlations. Decreased global efficiency also found level. These findings may provide insights into complex relationships among QSM, AD.

Язык: Английский

Процитировано

7
Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies DOI
Sebastian Niclas Roemer, Matthias Brendel, Johannes Gnörich

и другие.

Brain, Год журнала: 2024, Номер 147(7), С. 2428 - 2439

Опубликована: Июнь 6, 2024

Abstract Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent progressive supranuclear palsy (PSP) and corticobasal degeneration subcortical cortical neuronal dysfunction, as shown PET-assessed hypoperfusion glucose hypometabolism. Yet, there is a spatial mismatch between deposition patterns it unclear how these two pathological brain changes interrelated. Here, we hypothesized that pathology induces remote dysfunction in functionally connected regions to test pathophysiological model mechanistically links tauopathies. We included 51 Aβ-negative patients with clinically diagnosed PSP variants (n = 26) or syndrome 25) who underwent structural MRI 18F-PI-2620 tau-PET. tau-PET was recorded using dynamic one-stop-shop acquisition protocol determine an early 0.5–2.5 min post tracer-injection perfusion window for assessing well 20–40 4R-tau load. Perfusion-PET (i.e. window) assessed 200 regions, 32 established functional atlases. determined epicentres the highest signal connectivity interest resting-state MRI-based template derived from 69 healthy elderly controls ADNI cohort. Using linear regression, whether: (i) higher associated reduced perfusion; (ii) reductions were observed preferentially closely epicentres. As hypothesized, overall lower perfusion, which remained consistent when controlling group-average subject-level PET data, found seed-based pattern aligned patterns, where more epicentre showed perfusion. Together, tau-accumulation indicative 4R-tauopathies. This suggests may induce contribute clinical disease manifestation heterogeneity.

Язык: Английский

Процитировано

7
Curcumin as a potential therapeutic agent for treating neurodegenerative diseases DOI Creative Commons

Valeria Perales-Salinas,

Sushmitha S. Purushotham,

Yossi Buskila

и другие.

Neurochemistry International, Год журнала: 2024, Номер 178, С. 105790 - 105790

Опубликована: Июнь 7, 2024

Neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function, posing a tremendous burden on health systems worldwide. Although underlying pathological mechanisms for various neurodegenerative still unclear, common hallmark is abundance neuroinflammatory processes, which affect both disease onset progression. In this review, we explore pathways role neuroinflammation in further assess potential use curcumin, natural spice with antioxidant anti-inflammatory properties that has been extensively used worldwide as traditional medicine therapeutic agent. Following examination preclinical clinical studies assessed curcumin agent, highlight bioavailability body discuss challenges benefits using compound treating neurodegeneration. elucidating involvement aging neurodegeneration great developing future CNS-related targets, research required to elucidate Curcumin affects brain physiology, especially BBB integrity, under physiological conditions.

Язык: Английский

Процитировано

6
Tau follows principal axes of functional and structural brain organization in Alzheimer’s disease DOI Creative Commons
Julie Ottoy, Min Su Kang,

Jazlynn Xiu Min Tan

и другие.

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

Опубликована: Июнь 12, 2024

Abstract Alzheimer’s disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that distribution tau reactive microglia humans follows spatial patterns variation, so-called gradients organization. Notably, less distinct (“gradient contraction”) are associated with decline regions greater tau, suggesting an interaction between reduced differentiation on cognition. Furthermore, by modeling subject-specific gradient space, demonstrate frontoparietal temporo-occipital cortices baseline within their functionally structurally connected hubs, respectively. Our work unveils for both functional structural organization pathology AD, supports space as promising tool to map progression.

Язык: Английский

Процитировано

6