Quantification of perforant path fibers for early detection of Alzheimer's disease

Abstract

Introduction: The entorhinal cortex (ERC) and perforant path (PP) fibers are critical structures in the pathology of Alzheimer's disease (AD). This study aims to explore these regions using high-field magnetic resonance imaging (MRI), with the goal of identifying reliable biomarkers based on histopathological observations.

Methods: Twenty post mortem brain specimens were scanned with 11.7T MRI, including diffusion tensor imaging and tractography, and were cut for subsequent histological examinations. The entorhinal cortical thickness and number of PP fibers derived from MRI were compared across neuropathological and premortem clinical diagnoses of AD.

Results: The entorhinal cortical thickness and number of PP fibers decreased along with severities of neurofibrillary tangles in the ERC. Meanwhile, a reduction in the number of PP fibers, but not the entorhinal cortical thickness, was observed during the preclinical stage of AD.

Conclusions: Degeneration of PP fibers was observed in early AD and progressed along with neuropathological changes.

Highlights: Twenty post mortem brain tissues were scanned with 11.7T MRI. Degeneration of PP fibers was observed at 250 µm isotropic resolution. PP fiber indices were linked with severities of NFTs. The number of PP fibers was decreased in preclinical AD.

Keywords: Alzheimer's disease; diffusion tensor imaging; entorhinal cortex; histology; magnetic resonance imaging; neurodegeneration; perforant path; tractography.