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Alzheimer's Disease: Overview01:26

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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
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Alzheimer's disease (AD) alters brain functional gradients, impacting connectivity across networks. These changes correlate with specific biological processes, offering new insights into AD's neurological basis.

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Area of Science:

  • Neuroscience
  • Neuroimaging
  • Systems Neuroscience

Background:

  • Macroscale functional gradients map brain connectivity from unimodal to transmodal regions.
  • Alterations in these gradients in Alzheimer's disease (AD) and their relationship with cognitive and genetic factors are not well understood.

Purpose of the Study:

  • To investigate AD-associated changes in functional brain gradients using functional MRI data.
  • To explore correlations between altered functional gradients, cognitive terms, and gene expression profiles in AD.

Main Methods:

  • Utilized functional MRI data from seven scanners.
  • Employed data-driven meta-analytic techniques to identify AD-related gradient alterations.
  • Analyzed Gene Ontology terms for enriched biological processes.

Main Results:

  • The primary primary-to-transmodal functional gradient was suppressed in AD patients.
  • AD patients showed global connectome gradient alterations: reduced range and variation.
  • Increased gradient scores were observed in somatomotor, ventral attention, and frontoparietal regions; decreased scores in the default mode network.
  • Enrichment analysis revealed significant Gene Ontology terms related to potassium ion transport and protein-containing complex remodeling.

Conclusions:

  • Functional gradient alterations are a key feature of Alzheimer's disease connectome changes.
  • These findings provide a novel perspective on the neurobiological underpinnings of AD.
  • Identified biological processes offer potential targets for understanding AD pathogenesis.