DTI-ALPS Is Associated with Temporolimbic Amyloid but Not Plasma p-Tau181 Across the Alzheimer's Disease Continuum

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive aggregation of misfolded proteins. Accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) is the hallmark pathology of AD. Diffusion tensor imaging along the perivascular spaces (DTI-ALPS) has been proposed as an MRI marker related to perivascular diffusivity patterns and has been used in studies of neurodegenerative disease.

This study investigates the association between the association between DTI-ALPS indices, regional amyloid-PET burden, and plasma p-tau181 across the AD spectrum.

Data from 410 individuals was enrolled from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. DTI-ALPS was used as an imaging proxy related to perivascular diffusivity patterns.

Mean DTI-ALPS declined progressively from healthy controls to AD. Moreover, females reflected higher DTI-ALPS indices compared with males. No significant associations were observed between perivascular diffusivity patterns and plasma concentration of p-tau 181 in patients with cognitive decline. In contrast, the global cortical amyloid-PET SUVR was associated with the mean [β = -0.163] and right DTI-ALPS indices in the MCI group [β = -0.202]. Moreover, we observed stronger associations between DTI-ALPS index and amyloid-PET SUVR in the temporal pole cortex [β = -0.199], entorhinal cortex [β = -0.224], and parahippocampal gyrus in patients with MCI [β = -0.281].

Reduced DTI-ALPS indices were associated with increased temporolimbic amyloid deposition, particularly in individuals with MCI. These findings suggest DTI-ALPS-derived perivascular diffusivity as an imaging marker associated with amyloid burden in prodromal AD.