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Decreased CSF clearance and increased brain amyloid in Alzheimer's disease

Yi Li1, Henry Rusinek2, Tracy Butler3

  • 1Department of Radiology, Weill Cornell Medicine, Cornell University, Brain Health Imaging Institute, 407 East 61 Street, New York, NY, 10021, USA. yil4008@med.cornell.edu.

Fluids and Barriers of the CNS
|March 15, 2022
PubMed
Abstract

Insights

Impaired cerebrospinal fluid (CSF) clearance is linked to amyloid-beta (Aβ) deposition in Alzheimer's disease (AD). This study shows reduced CSF clearance in AD patients, correlating with Aβ levels and cognitive decline.

Area of Science:

  • Neuroscience
  • Neurology
  • Radiology

Background:

  • Alzheimer's disease (AD) is associated with brain amyloid-beta (Aβ) deposition, potentially due to impaired Aβ clearance.
  • Cerebrospinal fluid (CSF) clearance, a key component of brain glymphatic clearance (BGC), is abnormal in AD models.
  • Previous studies suggest reduced CSF flow in AD patients using MRI and PET tracers.

Purpose of the Study:

  • To investigate the relationship between CSF clearance and Aβ deposition in living humans with AD.
  • To quantify CSF clearance using novel PET tracers and assess its correlation with Aβ load, brain structure, and cognitive function.

Main Methods:

  • Utilized two PET tracers, 18F-THK5351 and 11C-PiB, to estimate ventricular CSF clearance.
  • Analyzed early dynamic PET frames in 9 normal controls and 15 AD participants.
  • Correlated CSF clearance measures with brain Aβ load, cortical thickness, and cognitive performance.

Main Results:

  • Ventricular CSF clearance was significantly reduced in AD patients by 18% (18F-THK5351) and 27% (11C-PiB).
  • Reduced CSF clearance strongly correlated with increased brain Aβ load (r = -0.66, p < 0.01).
  • Lower CSF clearance was associated with reduced cortical thickness and poorer cognitive performance.

Conclusions:

  • Failed CSF clearance is a significant feature of Alzheimer's disease, directly related to Aβ deposition.
  • These findings support the hypothesis that impaired CSF clearance contributes to AD pathology.
  • Further longitudinal studies are required to determine if failed CSF clearance predicts or results from amyloidosis.

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