Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: 139, P. 111375 - 111375

Published: April 23, 2025

Language: Английский

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BOLD Amplitude Correlates of Preclinical Alzheimer’s Disease

Neurobiology of Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 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

Language: Английский

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Precuneus activity during retrieval is positively associated with amyloid burden in cognitively normal olderAPOE4carriers

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract The precuneus is an early site of amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal Alzheimer’s disease (AD) risk stages are lacking and the interaction Apolipoprotein-E ( APOE ) genotype unclear. In PREVENT-AD cohort, we assessed how during successful memory retrieval at baseline over time relates to future Aβ tau burden change performance. We further studied moderation by APOE4 genotype. included 165 (age: 62.8±4.4 years; 113 female; 66 carriers) who were cognitively normal had a family history AD. All participants performed task-fMRI underwent 18 F-flortaucipir-PET F-NAV4694-Aβ-PET on average 5 years later. found that higher greater associated subsequent 4 carriers but not non-carriers. There no effects burden. Finally, non-carriers low exhibited better performance independent test compared high carriers. Our findings suggest task-related results indicate absence hyperactivation allele related best outcome for Significance Statement brain region involved episodic function Alterations occur ageing as well pathology even symptoms; however, their course implications understood. demonstrate its after Apolipoprotein-E4 APOE4) Lower activation was provide novel evidence posterior midline regions linked AD dependence

Language: Английский

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APOE4 Increases Susceptibility to Amyloid, Accelerating Episodic Memory Decline

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Individuals with one copy of APOE4 exhibit greater amyloid-beta (Aβ) deposition compared to noncarriers, an effect that even more pronounced in homozygotes. Interestingly, carriers not only show AD pathology but also experience rapid cognitive decline, particularly episodic memory. The underlying mechanisms driving this domain-specific vulnerability, however, remain unclear. In study, we examined whether accelerated decline memory among due increased Aβ or heightened susceptibility Aβ-related effects. Using data from Disease Research Initiative, modeled amyloid duration, estimated number years individual has been amyloid-positive, and its impact on trajectories. Our findings reveal associated as a function duration. This was dose-dependent, homozygotes declining rapidly than heterozygotes, it consistently observed across multiple tasks measures. Importantly, pattern other domains, such processing speed, executive function, visuospatial skills, language, crystallized intelligence. These results suggest trajectories differ by APOE genotype, conferring vulnerability hippocampal dysfunction early course. Future research should investigate these differences stem distinct pathological cascades carriers.

Language: Английский

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Differential effects of aging, Alzheimer’s pathology, andAPOE4on longitudinal functional connectivity and episodic memory in older adults

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract INTRODUCTION Both aging and Alzheimer’s disease (AD) affect episodic memory networks. How this relates to region-specific early differences in functional connectivity (FC), however, remains unclear. METHODS We assessed resting-state FC strength the medial temporal lobe (MTL) - posteromedial cortex (PMC) prefrontal network cognition over two years cognitively normal older adults from PREVENT-AD cohort. RESULTS within PMC between posterior hippocampus inferomedial precuneus decreased “normal” (amyloid- tau-negative adults). Lower was associated with poorer longitudinal performance. Increasing anterior superior related higher baseline AD pathology. Higher differentially trajectories depending on APOE4 genotype. DISCUSSION Findings suggest differential effects of pathology FC. MTL-PMC hypoconnectivity cognitive decline. Furthermore, hyperconnectivity decline carriers. Graphical abstract. A) “Normal aging” is characterized by a decrease connectivity. B) Cognitively unimpaired more at (measured via cerebrospinal fluid) exhibit increase

Language: Английский

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