Magnetic resonance imaging indices for early Alzheimer’s disease detection: Brain clearance markers

The Alzheimer's disease (AD) continuum is characterized by amyloid and tau protein deposition, which is partly attributable to the dysfunction of the brain clearance system. However, the specific phase in the AD continuum wherein aberrant clearance is present remains unclear. This study aimed to assess noninvasive magnetic resonance imaging (MRI) indices related to brain clearance functions, such as choroid plexus volume (CPV), lateral ventricular volume (LVV), and the index of diffusivity along the perivascular space (ALPS index), across the Alzheimer's disease (AD) spectrum. The CPV, LVV, and ALPS index in amyloid beta (Aβ)-negative healthy controls (HCs) and Aβ-positive HCs as well as in patients with Aβ-negative subjective cognitive decline (SCD), with Aβ-positive SCD, with mild cognitive impairment, and with AD were evaluated. The CPV and LVV were higher, whereas the ALPS index was lower in the patients with more severe disease. The ALPS index was significantly lower in Aβ-positive HCs than in Aβ-negative HCs. In SCD patients and those in the AD continuum, the MRI-based clearance markers were correlated with P-tau and T-tau protein levels and cognitive scores. In summary, brain clearance markers on MRI are associated with tau deposition, neurodegeneration and cognitive dysfunction.