Premium
Hypercholesterolemia accelerates Aβ deposition in regions associated with early amyloidosis
Author(s) -
Souza João Pedro Ferrari,
Povala Guilherme,
Brum Wagner Scheeren,
De Bastiani Marco Antônio,
Pascoal Tharick A.,
Benedet Andréa Lessa,
Therriault Joseph,
das Ros Lucas U.,
Bieger Andrei,
RosaNeto Pedro,
Zimmer Eduardo R.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044114
Subject(s) - cholesterol , medicine , pittsburgh compound b , alzheimer's disease neuroimaging initiative , amyloid (mycology) , neuroimaging , apolipoprotein e , amyloidosis , epidemiology , risk factor , dementia , endocrinology , disease , gastroenterology , pathology , psychiatry
Background Hypercholesterolemia is a well‐established risk factor for developing Alzheimer's disease (AD). Mechanisms underlying this relationship, however, are still unclear. Recent experiments have reported conflicting findings regarding the relationship between amyloid‐beta (Aβ) and cholesterol. While in vitro studies have shown that cholesterol accelerates Aβ aggregation, an epidemiological investigation demonstrated that total serum cholesterol is not associated with Aβ load. Nevertheless, it is still unclear whether total serum cholesterol affects Aβ deposition in the human brain. Here, we aimed to assess whether high levels of total serum cholesterol are associated with the rate of Aβ aggregation in the brain. We hypothesized that high total serum cholesterol levels could accelerate cerebral amyloidosis of non‐demented subjects. Method We selected 207 non‐demented – cognitively unimpaired and mild cognitive impairment – participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) who had available data for baseline cholesterol and longitudinal amyloid PET scans with [ 18 F]AV45. Subjects were divided into two groups regarding their total serum cholesterol levels, being classified as normal (<200mg/dL; n=158) or abnormal (>200mg/dL; n=107). We performed a voxel‐wise general linear modelling to assess Aβ load differences between groups at baseline. Then, a longitudinal comparison was carried out to evaluate the rate of Aβ deposition in 4 years, calculated as "(IMAGE 4_YEARS ‐ IMAGE BASELINE )x100/IMAGE BASELINE ". Age, gender, APOEε4, cholesterol treatment and diagnostic group were used as covariates. Result No differences were found in Aβ load at baseline. By contrast, we observed a significantly higher rate of Aβ accumulation for the abnormal group in brain regions associated to early amyloidosis, including lateral temporal (peak t(200) = 4.498, p<0.0001) and parietal (peak t(200) = 4.504, p<0.0001) lobes, over a 4‐year period when compared to the normal group (Figure 1). Conclusion Our findings suggest that serum cholesterol dysmetabolism could influence cerebral Aβ aggregation. In addition, our analysis points to a potential communication between central and peripheral cholesterol compartments (perhaps intensified by hypercholesterolemia‐related inflammation). Also, it corroborates with the hypothesis that higher serum cholesterol levels accelerate the process of brain amyloidosis, stressing the need for further investigation on the mechanisms involved in this process.