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

Background: 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. Aims: This study investigates the association between the association between DTI-ALPS indices, regional amyloid-PET burden, and plasma p-tau181 across the AD spectrum. Methods: 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. Results: 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]. Conclusions: 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.