Revisiting the ALPS index: Structural Bias on the Glymphatic Interpretation as revealed by post-mortem AD brains

Motivation: Diffusion tensor imaging based on analysis along the perivascular space (DTI-ALPS) has been used to assess glymphatic function. However, the underlying mechanism for ALPS change remains controversial. Goal(s): To improve understanding of ALPS from the perspective of structural bias. Approach: We hypothesized that ALPS reveals total water movement including flowing fluid and restricted diffusion in white matter structure. Post-mortem brains where no flow presented were used to examine the structural contribution to the ALPS. Results: Structural bias of ALPS was related to AD pathology and aging. Correction for the bias on ALPS weakens its correlation with AD-related indicators. Impact: The study explored ALPS in post-mortem AD brains from the perspective of structural bias. The underlying mechanism of ALPS alternation, whether the structure or physiology matters, should be interpreted cautiously. This study provides post-mortem and in-vivo insights into the problem.