Cerebrospinal fluid biomarkers of Alzheimer’s disease are associated with carotid plaque score and hemodynamics in intra- and extra-cranial arteries on ultrasonography

Abstract

Carotid plaque score (PS) and hemodynamic abnormalities in intra- and extra-cranial arteries are related to Alzheimer’s disease (AD) progression. As these parameters are measured conveniently and non-invasively by ultrasonography, we examined their association with cerebral spinal fluid (CSF) AD biomarkers amyloid β (Aβ) and phosphorylated tau (p-tau). Carotid PS, mean flow velocity (MFV) in multiple intra- and extra-cranial arteries, CSF Aβ42 and p-tau, neurocognitive function (assessed by the Mini-Mental State Examination and Alzheimer’s Disease Assessment Scale-cognitive subscale, Japanese version), and blood lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride) were measured in AD patients (n = 42), mild cognitive impairment patients (n = 20), and cognitively normal controls (n = 18). The results were also compared among groups defined by PS range. After adjusting for blood lipids as covariates, Aβ42 was higher in the PS = 1.1−2.0 mm group than in the higher PS groups (2.1−3.0, 3.1−5.0, 5.1−7.0, and >7.0 mm). However, subjects with very low PS (<1.1 mm) also had a low mean CSF Aβ42. Alternatively, CSF p-tau181 did not differ between PS groups. In multiple regression analysis, Aβ42 was not associated with MFVs; however, CSF p-tau181 showed a significant association with the MFV of the internal carotid and basilar arteries. Findings suggest that carotid plaque formation may accelerate Aβ42 deposition, although it is not necessary for deposition. Hemodynamics abnormalities may cause increased CSF p-tau181. Ultrasonographic evaluation of PS and arterial hemodynamics may be a useful noninvasive method for estimating AD pathology.