The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease

Manuello, Jordi; Min, Joosung; McCarthy, Paul; Alfaro-Almagro, Fidel; Lee, Soojin; Smith, Stephen; Elliott, Lloyd T.; Winkler, Anderson M.; Douaud, Gwenaëlle

doi:10.1038/s41467-024-46344-2

Cited by 2 publications

(1 citation statement)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic factors play a significant role in AD, especially in early-onset cases. Mutations in genes such as APP, PSEN1, and PSEN2 are associated with familial forms of AD, leading to increased production of Aβ [ 74 , 75 ].…”

Section: Sem Potential Mechanism Of Action In Admentioning

confidence: 99%

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Meca,

Boboc,

Mititelu-Tartau

et al. 2024

CIMB

View full text Add to dashboard Cite

Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review provides a comprehensive description of SEM’s mechanism of action and its effects in preclinical studies of these debilitating conditions. In animal models of AD, SEM has proved beneficial effects on multiple pathological hallmarks of the disease. SEM administration has been associated with reductions in amyloid-beta plaque deposition and mitigation of neuroinflammation. Moreover, SEM treatment has been shown to ameliorate behavioral deficits related to anxiety and social interaction. SEM-treated animals exhibit improvements in spatial learning and memory retention tasks, as evidenced by enhanced performance in maze navigation tests and novel object recognition assays. Similarly, in animal models of PD, SEM has demonstrated promising neuroprotective effects through various mechanisms. These include modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis. Additionally, SEM has been shown to improve motor function and ameliorate dopaminergic neuronal loss, offering the potential for disease-modifying treatment strategies. Overall, the accumulating evidence from preclinical studies suggests that SEM holds promise as a novel therapeutic approach for AD and PD. Further research is warranted to elucidate the underlying mechanisms of SEM’s neuroprotective effects and to translate these findings into clinical applications for the treatment of these devastating neurodegenerative disorders.

show abstract

Section: Sem Potential Mechanism Of Action In Admentioning

confidence: 99%

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Meca,

Boboc,

Mititelu-Tartau

et al. 2024

CIMB

View full text Add to dashboard Cite

show abstract

Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms

Khan,

Iturria-Medina

2024

Transl Psychiatry

View full text Add to dashboard Cite

From Alzheimer’s disease to amyotrophic lateral sclerosis, the molecular cascades underlying neurodegenerative disorders remain poorly understood. The clinical view of neurodegeneration is confounded by symptomatic heterogeneity and mixed pathology in almost every patient. While the underlying physiological alterations originate, proliferate, and propagate potentially decades before symptomatic onset, the complexity and inaccessibility of the living brain limit direct observation over a patient’s lifespan. Consequently, there is a critical need for robust computational methods to support the search for causal mechanisms of neurodegeneration by distinguishing pathogenic processes from consequential alterations, and inter-individual variability from intra-individual progression. Recently, promising advances have been made by data-driven spatiotemporal modeling of the brain, based on in vivo neuroimaging and biospecimen markers. These methods include disease progression models comparing the temporal evolution of various biomarkers, causal models linking interacting biological processes, network propagation models reproducing the spatial spreading of pathology, and biophysical models spanning cellular- to network-scale phenomena. In this review, we discuss various computational approaches for integrating cross-sectional, longitudinal, and multi-modal data, primarily from large observational neuroimaging studies, to understand (i) the temporal ordering of physiological alterations, i(i) their spatial relationships to the brain’s molecular and cellular architecture, (iii) mechanistic interactions between biological processes, and (iv) the macroscopic effects of microscopic factors. We consider the extents to which computational models can evaluate mechanistic hypotheses, explore applications such as improving treatment selection, and discuss how model-informed insights can lay the groundwork for a pathobiological redefinition of neurodegenerative disorders.

show abstract

The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease

Cited by 2 publications

References 60 publications

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms

Contact Info

Product

Resources

About