Basal forebrain nuclei volume is associated with hematoencephalic barrier dysfunction in early Alzheimer’s disease

Abstract

AbstractBackgroundHematoencephalic barrier (HEB) is a protective layer of cells that separates the circulatory system from the brain. Its dysfunction is one of the possible mechanisms leading to the development of Alzheimer’s disease (AD), a progressive neurodegenerative disease and a leading cause of dementia worldwide. The albumin quotient (QAlb), the ratio between cerebrospinal fluid (CSF) and serum albumin concentrations, is a frequently used measure of HEB breakdown. Elevated levels of QAlb were previously reported in early AD. Here we explored the relationship between QAlb and volumes of the hippocampus and entorhinal cortex (EC) subregions and basal forebrain (BF) nuclei, the brain structures affected early in the course of AD.Method92 participants, including 20 AD biomarker negative cognitively normal (CN), 42 AD biomarker positive with mild cognitive impairment (AD‐MCI) and 30 AD biomarker positive with mild dementia (AD‐DEM), from the Czech Brain Aging Study underwent structural MRI and CSF sampling. CSF levels of amyloid beta 1‐42, total tau, phosphorylated tau 181 and QAlb, as well as volumes of the hippocampal subregions (i.e., head, body and tail), anterolateral and posteromedial EC and BF nuclei were obtained. Associations between regional brain volumes, normalized to total intracranial volume, and QAlb were assessed using MANOVA controlled for gender and age.ResultIn the AD‐MCI group, volumes of the anterior and posterior parts of the nucleus basalis of Meynert (NBM), one of the BF nuclei, were positively associated with QAlb levels (β = 0.317 and 0.345, p = 0.045 and 0.029, respectively). There were no other significant associations of regional brain volumes with QAlb in CN, AD‐MCI or AD‐DEM groups. All measured volumes, except for BF nuclei of medial septum in AD‐DEM (p = 0.058), were smaller in AD‐MCI and AD‐DEM v.s. CN group (p<0.05). There were no differences in volumes between AD‐MCI and AD‐DEM groups. QAlb did not differ between groups.ConclusionOur results show that severity of HEB dysfunction is associated with increased volume of the NBM in individuals with AD‐MCI, suggesting a link between HEB dysfunction and early pathological changes in the BF nuclei.