A group of Queen Square Dementia Biomedical Research Unit (BRU) researchers has further characterised the wasting atrophy patterns in familial Alzheimer’s Disease (AD), paving the way for developing more sensitive methods for tracking the disease and managing the disease before its onset.
The spatial pattern of atrophy is one of the most accurate markers of the disease’s progression, and in this cross-sectional study, researchers used a method called voxel based morphometry (VBM) to assess the pattern.
Dr David Cash, co-lead author on the paper published in Neurology, said: “VBM is particularly useful when you want to examine the whole brain. Following some pre-processing on the MRI brain scans you get a sense of how much grey matter – the computational hubs, and white matter - the cabling, there is. Effectively, within each voxel, a 3D cube of data, we can get a measure of how much grey matter there is”.
He continued; “As the brain sizes and shapes are different for different subjects, we warp the images to align the brains, and then run statistical analysis in each voxel to see if changes are occurring in specific parts of anatomy”.
Analysis revealed three key changes in grey and white matter and in the thalamus. Dr Cash indicated the importance the changes in terms of the role the brain regions play “The brain has a default mode network, which some of these regions belong to and which often shows early signs of AD pathology in the form of accumulation of amyloid plaques; the disease also appears to propagate through these networks. Changes in these affected areas are linked with changes in executive and memory function.”
Familial AD, unlike more common sporadic AD, is associated with specific gene mutations that cause the cascade of amyloid plaque generation and other pathologies linked to AD, typically at an earlier age than for sporadic AD. There are 3 main genes involved: presenilin 1 (which causes 80% of familial AD cases), presenilin 2, and APP.
Co-lead author Dr Ridgway added “a key question at this stage is whether the pattern of atrophy in familial AD differs from that in the sporadic disease; our findings of atrophy in the thalamus and putamen, together with previous amyloid imaging studies, suggest that this might be the case, but direct comparison with sporadic AD (using the same methods, and scans as similar as possible) will be needed to confirm this.”
Dr Cash emphasized: “The unique scale of this study thanks to the international collaboration known as DIAN (Dominantly Inherited Alzheimer Network) allows the demonstration of definitive signals across a wider range of mutation over a wider range of sites, allowing us to look across key regions of the brain, regardless of second order issues, for which VBM sets the roadmap for picking up pre-symptomatic change in the brain”.
Professor Rossor, BRU Director and co-author, commented on the value of large multinational collaborations like DIAN which provided the numbers of participants needed for this type of study: “The study builds on the DIAN data which has shown a significant period of disease development prior to functional decline, a period which provides a “window of opportunity” for therapeutic intervention”.
