O2‐05‐01: Clusterin, an amyloid chaperone protein in plasma is associated with longitudinal brain atrophy in mild cognitive impairment
Year: 2010
Type: article
Abstract: We recently reported that plasma concentration of clusterin was associated with severity, neuropathology and clinical progression in Alzheimer's disease (AD). Moreover, the largest genome wide association studies to date have recently identified polymorphisms in the clusterin gene that are associated with risk of AD. We examined the association between plasma clusterin concentration and longitudinal changes in brain volume in individuals with mild cognitive impairment (MCI) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. Non-demented individuals (N = 139; baseline age 57-87 years) were assessed annually with volumetric MRI over a mean six-year interval. Sixteen participants were diagnosed with amnestic MCI over the course of the study. Clusterin concentration was assayed in plasma samples collected within a year of the baseline MRI scan using a commercially available ELISA kit. Mixed effects regression models compared differences in the association of plasma clusterin concentration with rates of change of regional brain volumes between control and MCI groups based on more than 900 observations. Control and MCI groups did not differ in baseline clusterin concentration. The MCI group showed significantly higher rates of atrophy relative to controls in whole brain volume, ventricular CSF (vCSF), total, frontal and temporal gray matter as well as hippocampus and entorhinal cortex. The association of plasma clusterin concentration with rates of change in brain volume was significantly different between MCI and control groups in several global and lobar volumes including whole brain, vCSF, and temporal gray matter. Similar differences were observed in the parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, we observed a significant association between plasma clusterin concentration and rates of atrophy in the above regions. In these regions, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in MCI. Clusterin, a plasma protein with roles in amyloid clearance, complement inhibition and apoptosis is associated with rate of brain atrophy in MCI. Although the mechanisms underlying this relationship remain to be investigated, our results suggest a possible disease-modifying effect of clusterin in early stages of AD pathology.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2170891509