Quantitative Assessment of Cerebrospinal Fluid-Vascular Association in Alzheimer's Disease Using Phase-Contrast and 4D-Flow Magnetic Resonance Imaging.

Abstract

From a neuropathological perspective, the most well-known pathological change in Alzheimer's disease (AD) to date is primarily tau protein hyperphosphorylation, which leads to the formation of intracellular neurofibrillary tangles (NFTs) and amyloid protein deposition-namely, the accumulation of amyloid protein (Aβ) and other protein aggregates outside cells, resulting in neurofibrillary tangles. The glymphatic system, driven by arterial pulsation, clears waste, including amyloid-β, via perivascular spaces (PVS). In AD, vascular dysfunction and slow-wave sleep speculation have been separately observed, and both are hypothesized to impair glymphatic clearance. However, causal links among these factors remain unproven, and the proposed self‑reinforcing cycle-where vascular failure may aggravate protein deposition and further vascular damage-is speculative. This study utilized two-dimensional cine phase-contrast MRI (PC-MRI) and four-dimensional flow MRI (4D-Flow) to quantify hydrodynamic parameters, including cerebrospinal fluid (CSF) flow in the cerebral aqueduct (CA) and blood flow in the internal carotid artery (ICA). Altered CSF-vascular association was observed in AD, suggesting possible glymphatic involvement. The integration of CSF and vascular flow metrics provides a promising biomarker framework for early AD detection and monitoring. PC-MRI and 4D-Flow reveal altered CSF-vascular association in Alzheimer's disease, reflecting potential glymphatic alteration and offering a non-invasive, quantitative method for potential adjunctive biomarker and disease monitoring.