Dti-Alps Index and Its Association With Neuroinflammatory and Neurodegenerative Biomarkers and Tau-Pet in Alzheimer's Continuum Publisher Pubmed



Zafari R ; Kamroo A ; Taherkhani T ; Nabizdeh F ; Aarabi M H
Source: Neuroscience Published:2026

Abstract

Glymphatic dysfunction may contribute to abnormal protein accumulation in Alzheimer's disease (AD). This study investigates associations between an indirect proxy of glymphatic function, plasma neurodegenerative and neuroinflammatory biomarkers, and tau-PET burden across the AD continuum. Data from 407 ADNI participants were utilized. Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) is used as a noninvasive proxy of glymphatic activity. Multivariable linear regression models were applied to assess associations between DTI-ALPS indices and biomarkers, adjusting for age, sex, years of education, APOE ε4 status, and mean diffusivity. Mean DTI-ALPS index declined from healthy controls to AD. There was a significant association between the mean DTI-ALPS index and plasma levels of p-tau 217 and Aβ40 in healthy participants. Moreover, the DTI-ALPS index in the left hemisphere was negatively associated with Aβ42 among patients with MCI. Additionally, a significantly negative association was found between plasma concentrations of NfL and both the mean and right DTI-ALPS indices in the MCI group. We observed similar associations between GFAP concentrations and the mean and right DTI-ALPS indices in patients with MCI. Moreover, the mean DTI-ALPS index was negatively associated with tau burden in Braak stages I-II, III, IV, and V across all participants. Overall, DTI-ALPS indices, as indirect imaging proxy of the glymphatic system, are linked to AD-related neuroinflammatory and neurodegenerative plasma and imaging biomarkers, particularly in early disease stages of the AD spectrum. These preliminary findings require cautious interpretation and replication to clarify the glymphatic system's relevance to neurodegeneration. © 2026 International Brain Research Organization (IBRO)