Intracranial stenosis and longitudinal progression of Alzheimer's disease pathologies

The relationship between intracranial stenosis (ICS) and Alzheimer's disease (AD) pathologies remains unclear. We investigated whether baseline ICS is associated with longitudinal changes in amyloid beta (Aβ) and tau deposition.

We prospectively followed 180 older adults (mean age 70.06 ± 7.40 years), including cognitively normal (CN) and cognitively impaired (CI) individuals. ICS was assessed with magnetic resonance angiography. Aβ and tau deposition were measured using Pittsburgh compound B positron emission tomography (PET) and AV-1451 PET, respectively. Participants were classified into Aβ and tau analysis groups, each including both CN and CI individuals, and separate models were constructed to evaluate associations between ICS and longitudinal changes in each biomarker.

The presence of any ICS was significantly associated with greater Aβ accumulation over 4 years, while ICS in two or more arteries predicted greater tau deposition over 2 years.

ICS may accelerate both Aβ and tau accumulation, supporting a vascular contribution to AD pathogenesis.

Intracranial stenosis at baseline predicts 4-year increase in amyloid beta deposition. Two or more stenotic intracranial arteries are linked to 2-year tau accumulation. Associations remain after adjusting for apolipoprotein E ε4 status and cognitive impairment. Intracranial atherosclerosis may accelerate both amyloid and tau accumulation.