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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.
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Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
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Changes in the language system as amyloid-β accumulates.

Mariska Reinartz1, Silvy Gabel1, Jolien Schaeverbeke1

  • 1Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium.

Brain : a Journal of Neurology
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Amyloid accumulation impacts language networks in cognitively intact older adults. This preclinical Alzheimer's disease finding shows changes in brain circuitry even before symptoms appear.

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18F-AV1451Alzheimer’s diseaseamyloid PETfMRIlongitudinal study

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Area of Science:

  • Neuroscience
  • Neurology
  • Cognitive Science

Background:

  • Language dysfunction is a common symptom of Alzheimer's disease (AD).
  • Early detection and understanding of preclinical AD are crucial for intervention.
  • The preclinical phase of AD involves pathological changes before cognitive decline is evident.

Purpose of the Study:

  • To investigate the association between amyloid accumulation and functional changes in the language network.
  • To examine how longitudinal functional MRI changes relate to tau load in cognitively intact individuals.
  • To identify early alterations in brain circuitry related to language in asymptomatic Alzheimer's disease.

Main Methods:

  • Longitudinal study design over 5-6 years in 35 cognitively intact older adults.
  • Amyloid accumulation measured using Positron Emission Tomography (PET).
  • Functional changes in the language network assessed using task-related functional MRI; tau load measured with 18F-AV1451 PET.

Main Results:

  • Amyloid accumulation correlated with increased response amplitude in the right superior temporal sulcus cortex during a semantic task.
  • Amyloid accumulation was associated with decreased response amplitude in the left inferior frontal sulcus and right dorsomedial prefrontal cortex.
  • No association was found between cross-sectional tau load and longitudinal functional MRI changes in this cohort.

Conclusions:

  • Neocortex surrounding the posterior superior temporal sulcus plays a key role in the earliest stages of Alzheimer's disease.
  • Amyloid accumulation affects cognitive brain circuitry during the asymptomatic phase of Alzheimer's disease.
  • These findings highlight the impact of early amyloid pathology on language network function in cognitively normal individuals.