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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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Real-space navigation testing differentiates between amyloid-positive and -negative aMCI.

Florian Schöberl1, Cauchy Pradhan1, Stephanie Irving1

  • 1From the Department of Neurology (F.S., J.E., P.W., A.Z., M.D.), University Hospital, German Center for Vertigo and Balance Disorders (F.S., C.P., S.I., G.X., G.K., S.K., E.S., K.J., C.l.F., P.B., T.B., M.D., A.Z.), DSGZ, Institute for Stroke and Dementia Research (K.B.), ISD, University Hospital, Department of Nuclear Medicine (G.X., M.B., P.B.), Department of Psychiatry (R.P.), and Clinical Neurosciences (T.B.), Ludwig Maximilian University of Munich; German Center for Neurodegenerative Diseases (K.B., R.P., M.D.), DZNE, Munich; Institute for Medical Technology (E.S.), Brandenburg University of Technology Cottbus-Senftenberg; Munich Cluster of Systems Neurology (R.P., P.B., M.D.), SyNergy, Germany; Ageing Epidemiology Research Unit (R.P.), School of Public Health, Imperial College, London, UK; Neurological Hospital (K.J.), Schön Klinik Bad Aibling; and Department of Nuclear Medicine (C.l.F.), Eberhard Karl University of Tübingen, Germany.

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Patients with amyloid-positive amnestic mild cognitive impairment (aMCI) show impaired navigation and reduced brain activation compared to amyloid-negative aMCI patients. Real-space navigation effectively identifies Alzheimer

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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Medical Imaging

Background:

  • Distinguishing between amyloid-positive (A+) and amyloid-negative (A-) amnestic mild cognitive impairment (aMCI) is crucial for understanding Alzheimer's disease pathology.
  • Mild cognitive impairment (MCI) affects memory and navigation, but the specific impact of amyloid pathology on these functions requires further investigation.
  • Current diagnostic methods may not fully capture the subtle cognitive and behavioral changes associated with early-stage Alzheimer's disease.

Purpose of the Study:

  • To differentiate A+ aMCI patients from A- aMCI patients using a multi-modal approach.
  • To investigate differences in navigation performance, visual exploration, and brain activation patterns between A+ and A- aMCI patients.
  • To assess the utility of real-space navigation tasks in identifying underlying Alzheimer's pathology in aMCI.

Main Methods:

  • Twenty-one aMCI patients were classified as A+ or A- based on PET imaging and CSF analysis.
  • Participants completed a real-space navigation task assessing egocentric and allocentric route planning strategies.
  • Navigation-induced brain activations were measured using 18F-fluorodeoxyglucose PET, and visual exploration was recorded via eye-tracking.

Main Results:

  • A+ aMCI patients exhibited significantly worse performance in both egocentric and allocentric navigation compared to A- aMCI patients and controls.
  • Both aMCI subgroups demonstrated reduced shortcut usage, slower movement, and prolonged time at crossings.
  • A+ patients showed diminished activation in the right hippocampus, retrosplenial cortex, and parietal cortex during navigation.

Conclusions:

  • Amyloid-positive aMCI is associated with more widespread impairment of the cerebral navigation network, impacting route planning.
  • Real-space navigation tasks show promise as a tool for identifying aMCI patients with underlying Alzheimer's pathology.
  • The findings highlight the potential of navigation-based assessments in early Alzheimer's disease detection.