DTI-ALPS index and its association with neuroinflammatory and neurodegenerative biomarkers and tau-PET in Alzheimer’s continuum

Rasa Zafari, Amirhossein Kamroo, Tina Taherkhani, Fardin Nabizdeh, Mohammad Hadi Aarabi
Neuroscience. 2026-08-01; 609: 101-115
DOI: 10.1016/j.neuroscience.2026.05.010

1. Neuroscience. 2026 Aug 17;609:101-115. doi:
10.1016/j.neuroscience.2026.05.010. Epub 2026 May 20.

DTI-ALPS index and its association with neuroinflammatory and neurodegenerative
biomarkers and tau-PET in Alzheimer’s continuum.

Zafari R(1), Kamroo A(2), Taherkhani T(2), Nabizdeh F(3), Aarabi MH(4); For
Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Author information:
(1)School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Electronic address: .
(2)School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
(3)School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
(4)Institut des Maladies Neurodégénératives, Groupe d’Imagerie
Neurofonctionnelle (GIN-IMN), Université de Bordeaux, Bordeaux, France.

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.

DOI: 10.1016/j.neuroscience.2026.05.010
PMID: 42167671 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors
declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.