Presenter of 1 Presentation
SMALL VESSELS-BIG PROBLEMS IN ALZHEIMER’S DISEASE
Abstract
Aims
Alzheimer’s Disease (AD) and vascular dementia (VaD) account for most cases of dementia. Although their etiology remains unclear, the major vascular cause of dementia is Cerebral Small Vessel Disease (CSVD). The diagnosis of CSVD relies on imaging findings on MRI. White matter hyperintensities (WMH) are the foremost common hallmark of CSVD. The aim of our study is to investigate the pathological mechanisms underlying WMH.
Methods
We conducted high-field (7 Tesla) MRI on human postmortem brains (n=24) of elderly people with chronic hypertension during life to assess CSVD burden, focusing on the analysis of WMH by Fazekas score severity and volumetry. After careful evaluation, brain axial biopsies were taken and (immuno-)histochemistry (IHC) was performed to assess neuroinflammation, vascular remodeling, (de-)myelination, and amyloid-β burden. To accurately co-register our MRI findings to IHC data, we developed a custom written MATLAB script to compare changes in WMH on MRI to microscopical changes in IHC.
Results
WMH were characterized by an increase in neuroinflammatory markers compared to surrounding normal appearing white matter (NAWM). Higher burden of WMH positively correlated to an increase of active microglial cells in WMH. Individuals with higher WMH burden showed increased loss of myelin, which was more pronounced in WMH than in NAWM. Blood vessels found in WMH were smaller than those found in NAWM.
Conclusions
Our study provides a unique opportunity to investigate neurodegenerative markers underlying MRI visible lesions at microscopical scale. Understanding CSVD hallmarks’ underlying pathology will shed light on possible biomarkers or potential treatment strategies for CSVD, and subsequently AD.