Selectively vulnerable deep cortical layer 5/6 fast-spiking interneurons in Alzheimer’s disease models in vivo DOI Creative Commons
Amalia Papanikolaou, David Graykowski, Byung Il Lee

и другие.

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Alzheimer's disease (AD) is initiated by amyloid-beta (Aβ) accumulation in the neocortex; however, cortical layers and neuronal cell types first susceptible to Aβ remain unknown. Using vivo two-photon Ca2+ imaging visual cortex of AD mouse models, we found that layer 5 neurons displayed abnormally prolonged transients before substantial plaque formation. Neuropixels recordings revealed these abnormal were associated with reduced spiking impaired tuning parvalbumin (PV)-positive fast-spiking interneurons (FSIs) 5/6, whereas PV-FSIs superficial remained unaffected. These dysfunctions occurred alongside a deep-layer-specific reduction pentraxin 2 (NPTX2) within excitatory neurons, decreased GluA4 PV-FSIs, fewer synapses onto PV-FSIs. Notably, NPTX2 overexpression increased input 5/6 rectified their activity. Thus, our findings reveal an early selective impairment deep models identify deep-layer as therapeutic targets.

Язык: Английский

Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer’s spectrum DOI Creative Commons
Casey R. Vanderlip, Craig E.L. Stark

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 26, 2024

Abstract Digital cognitive assessments, particularly those that can be done at home, present as low burden biomarkers for participants and patients alike, but their effectiveness in diagnosis of Alzheimer’s or predicting its trajectory is still unclear. Here, we assessed what utility added value these digital assessments provide identifying high risk decline. We analyzed >500 ADNI who underwent a brief assessment Aβ/tau PET scans, examining ability to distinguish status predict Performance on the were superior both cortical Aβ entorhinal tau detecting mild impairment future decline, with mnemonic discrimination deficits emerging most critical measure decline accumulation. are effective at-risk individuals, supporting low-burden tools early detection monitoring.

Язык: Английский

Процитировано

4
Digital cognitive assessments as low‐burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer's spectrum DOI Creative Commons
Casey R. Vanderlip, Craig E.L. Stark

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(10), С. 6881 - 6895

Опубликована: Сен. 6, 2024

Abstract BACKGROUND Digital cognitive assessments, particularly those that can be done at home, present as low‐burden biomarkers for participants and patients alike, but their effectiveness in the diagnosis of Alzheimer's disease (AD) or predicting its trajectory is still unclear. Here, we assessed what utility added value these digital assessments provide identifying high risk decline. METHODS We analyzed >500 Disease Neuroimaging Initiative who underwent a brief assessment amyloid beta (Aβ)/tau positron emission tomography scans, examining ability to distinguish status predict RESULTS Performance on was superior both cortical Aβ entorhinal tau detecting mild impairment future decline, with mnemonic discrimination deficits emerging most critical measure decline accumulation. DISCUSSION are effective at‐risk individuals, supporting tools early AD detection monitoring. Highlights predicts progression higher proficiency compared tau. Deficits indicative Impaired inferior temporal

Язык: Английский

Процитировано

4
Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs? DOI Creative Commons

Lorenzo Pini,

Simone Lista, Alessandra Griffa

и другие.

Brain Communications, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 18, 2024

Abstract The preclinical phase of Alzheimer’s disease represents a crucial time window for therapeutic intervention but requires the identification clinically relevant biomarkers that are sensitive to effects disease-modifying drugs. Amyloid peptide and tau proteins, main histological hallmarks disease, have been widely used as anti-amyloid anti-tau However, these do not fully capture multiple biological pathways brain. Indeed, robust amyloid-target engagement by monoclonal antibodies has recently translated into modest cognitive clinical benefits in patients, albeit with potentially life-threatening side effects. Moreover, targeting pathway yet result any positive outcomes. Findings from computational neuroscience demonstrated brain regions work isolation interconnected within complex network structures. Brain connectivity studies suggest misfolded proteins can spread through connections, leading hypothesis is pathology disconnectivity. Based on assumptions, here we discuss how incorporating outcomes could better global functionality and, conjunction traditional biomarkers, facilitate development new anti-Alzheimer’s

Язык: Английский

Процитировано

4
Lower Network Functional Connectivity Is Associated With Higher Regional Tau Burden Among Those At-Risk of Alzheimer’s Disease But Cognitively Unimpaired: Specific Patterns Based on Amyloid Status DOI Creative Commons

Jamie Ford,

Rosaleena Mohanty, Eric Westman

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract Introduction: Functional connectivity within the medial temporal lobe (MTL) and default mode network (DMN) changes across Alzheimer's disease stages, influenced by influencing cortical amyloid-beta (Aβ) regional tau burden. Previous research highlights functional connectivity's role in Alzheimer’s progression interactions of Aβ between MTL DMN, but their impact on deposition remains largely unexplored. Methods: Cognitively unimpaired participants from OASIS-3 (AV1451 cohort, n=287) were classified into Aβ- (n=193) Aβ+ (n=94) groups via amyloid-PET for cross-sectional analyses. Principal components analysis identified two MTL-functional DMN-functional principal (PCs), which correlated with per Braak stages 1-6 brain regions. status-specific robust regressions evaluated whether was associated tau. Results: In participants, lower “MTL Integration Axis” (PC1) higher levels left entorhinal cortex. In elevated DMN’s lateral parietal cortex, MTL's right parahippocampal 3-6 Discussion: Decreased increased burden, showing effects. Enhancing could be a therapeutic strategy promising direction future clinical interventions.

Язык: Английский

Процитировано

0
Regional susceptibility of PV interneurons in an hAPP-KI mouse model of Alzheimer’s disease pathology DOI Creative Commons
Mercedes M. Gonzalez, Benjamin Magondu, Matthew JM Rowan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Early-stage Alzheimer's pathology correlates with disrupted neuronal excitability, which can drive network and cognitive dysfunction even prior to neurodegeneration. However, the emergence extent of these changes may vary by brain region cell types situated in those regions. Here we aimed investigate effects AD on different neuron subtypes both entorhinal cortex, a enhanced early AD, primary visual relatively unaffected early-stage AD. We designed employed semi-automated patch clamp electrophysiology apparatus record from fast-spiking parvalbumin interneurons excitatory neurons regions, recording over 150 cells young adult APP-KI mice. In amyloid overproduction resulted PV interneuron hypoexcitability, whereas were concurrently hyperexcitable. Conversely, either subclass largely cortex. Together, findings suggest that but not play an integral role progression.

Язык: Английский

Процитировано

0
Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s Disease DOI
Rikesh M. Rajani, Robert Ellingford,

Mariam Hellmuth

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 27, 2024

Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer’s Disease (AD), but the underlying assumption that neurons are main source pathogenic Aβ is untested. Here we challenge this prevailing belief by demonstrating oligodendrocytes an important Aβ, and play a key role promoting abnormal neuronal hyperactivity AD. We show selectively suppressing oligodendrocyte production improves AD brain pathology restores function vivo . Our findings suggest targeting could promising therapeutic strategy for

Язык: Английский

Процитировано

3
Structural and functional remodeling of neural networks in β-amyloid driven hippocampal hyperactivity DOI
Jinquan Li, Yanjun Liu,

Chuhui Yin

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102468 - 102468

Опубликована: Авг. 31, 2024

Язык: Английский

Процитировано

3
Iron deposition is associated with motor and non-motor network breakdown in parkinsonism DOI Creative Commons

Fangda Leng,

Yue Gao, Fan Li

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 16

Опубликована: Янв. 20, 2025

Background Iron deposition has been observed in Parkinsonism and is emerging as a diagnostic marker for movement disorders. Brain functional network disruption also detected parkinsonism, believed to be accountable specific symptoms parkinsonism. However, how iron influences brain remains elucidated. Methods We recruited 16 Parkinson’s disease (PD), 8 multiple system atrophy (MSA) 7 progressive supranuclear palsy (PSP) patients. T1-weighted, susceptibility weighted images resting-state MRI (rs-fMRI) were acquired. Quantitative mapping (QSM) analysis was performed quantify substantia nigra, putamen dentate nucleus. Cerebellar network, sensorimotor default mode language networks segregated using independent analysis. Network status evaluated relation groups, motor non-motor symptoms. The relationship between quantitative further interrogated. To validate the findings, 13 healthy controls 37 PD patients who had available T1 rs-fMRI scans selected from progression markers initiative (PPMI) database, performed. Results In local cohort, compared PD, MSA showed greater putamen, while PSP caudate nucleus thalamus. significant difference across did not. significantly impaired cerebellar positively associated with symptom scores MoCA negatively both networks’ activity PPMI impairment found PD. correlated cognitive impairment, respectively. Conclusion are differently influenced MSA, PSP, which can serve potential marker. Impairment of Moreover, dysfunction deep nuclei (SN, DN, Putamen).

Язык: Английский

Процитировано

0
Disrupted astrocyte-neuron signaling reshapes brain activity in epilepsy and Alzheimer’s disease DOI
Mengjie Wu, Ruonan Zhang, Peng Fu

и другие.

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Differential effects of 2 and 4 weeks repetitive transcranial magnetic stimulation inducing neuroplasticity on cognitive improvement DOI Creative Commons
Xian Shi,

Wenao Zheng,

Xinle Hou

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Март 23, 2025

Background Repetitive transcranial magnetic stimulation (rTMS) is an efficient intervention for alleviating cognitive symptoms in Alzheimer's disease (AD), but the optimal treatment duration high efficacy remains unclear. Objective This study investigates effects of 2-week and 4-week rTMS on neural network plasticity improvement, aiming to identify impairment. Methods was administered cognitively impaired patients over periods, exploring its improvement induced circuits. The also examines predictive value these circuits individual responses. Results significantly outperformed course improving function. Neural activity analysis identified precuneus as a key region episodic memory. Changes brain regions, particularly within default mode (DMN), visual (VN), motor (MN), were associated with improvements. Baseline functional connectivity regions predicted changes general cognition (r = 0.724, p < 0.001) memory 0.447, 0.022) after rTMS. Conclusions Extended enhances performance impairment patients, showing superior effects. Reduced DMN following linked baseline can predict patients’

Язык: Английский

Процитировано

0