Here are some examples of the groundbreaking research that has taken place thanks to the generosity of brain donors and the support of Brains for Dementia Research:
Using tissue donated through Brains for Dementia Research (BDR), neuropathologists from around the UK have produced new criteria for the assessment of vascular dementia. Previous to this work, there was no widely accepted neuropathological criteria for the post-mortem diagnosis of vascular dementia, resulting in a wide variation in the definitions, sampling procedures and interpretation of vascular pathology. Working cooperatively, neuropathologists from the BDR network assessed vascular pathology and agreed on consensus criteria, named VCING (Vascular Cognitive Impairment Neuropathology Guidelines). They also identified which pathological markers best predicted cognitive impairment in vascular dementia. This work will standardise outputs from research in this area and allow for the establishment of improved post-mortem assessment criteria for vascular dementia.
[Vascular Cognitive Impairment Neuropathology Guidelines (VCING) – a multi-centre study of the contribution of cerebrovascular pathology to cognitive impairment. O Skrobot et al., Brain, 2016]
Researchers at the University of Southampton used brain tissue donated through Brains for Dementia Research to understand the role of inflammation in Alzheimer’s disease. Researchers now believe that inflammation plays a key part in causing nerve cell damage in Alzheimer’s and other causes of dementia, and are seeking ways to keep the immune system in check. The team in Southampton studied a type of immune cell in the brain called microglia. They found that there were more microglia in the brains of people with Alzheimer’s, compared to healthy people who died at a similar age. They also found that there were high levels of a protein that controls the number of microglia. This finding using human brain tissue prompted the team to start investigating whether blocking excess numbers of microglia could help protect nerve cells from damage in mice. Using this approach, they found that memory and thinking skills in mice improved and have now kick-started drug discovery efforts to find new treatments for Alzheimer’s.
[Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology. A Olmos-Alonso et al., Brain, 2016]
Work from the Guerreiro-Bras lab at UCL used tissue from Brains for Dementia Research to understand the genetic similarities between dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease. These three diseases have some overlapping symptoms and genetic associations, which means that it can sometimes be hard to make an accurate diagnosis. The researchers analysed tissue samples from people with each of these diseases to discover the extent of genetic overlap between them. The results showed that dementia with Lewy bodies shares roughly the same amount of genetic overlap with Alzheimer’s disease and Parkinson’s disease. This implies that, while dementia with Lewy bodies is distinct from both Alzheimer’s and Parkinson’s, it is strongly related to both diseases. This study could lead to an improvement of diagnostic techniques for each of these diseases.
[Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson’s and Alzheimer’s diseases. R Guerreiro et al., Neurobiology of Aging, 2015]
Tissue from Brains for Dementia Research was used in a study from UCL looking at the genes that are associated with risk of dementia with Lewy bodies (DLB). The researchers analysed tissue from over 788 people who had a diagnosis of DLB and compared this to over 2600 samples from people who didn’t have the condition. The results confirmed previous findings that the genes APOE and SNCA are strong genetic risk factors for DLB. They also found variations in another gene, SCARB2, which were linked to the condition. The SCARB2 gene affects a part of the cell called the lysosome, which is responsible for removing unwanted or toxic proteins. This finding compliments previous results that found a link between DLB and another gene involved in lysosome function. Together, these findings indicate that the underlying mechanisms behind dementia with Lewy bodies may involve dysfunction of the lysosome.
[Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. J Bras et al., Human Molecular Genetics, 2014]
Thanks to support from BDR, researchers at the University of Exeter Medical School and King’s College London revealed that chemical tags to DNA, called ‘epigenetic changes’ could play a role in Alzheimer’s. These tags are thought to be one way that our environment can control our genetics and are a way for the body to fine tune the expression of genes. The team discovered that chemical changes to a gene called ANK1 were[ strongly linked to signs of Alzheimer’s in the brain, suggesting ANK1 to play a role in the disease. The team must now follow-up this important discovery to find out more about what ANK1 can reveal about the biology of the disease.
[Methylomic profiling implicated cortical deregulation of ANK1 in Alzheimer’s disease. K Lunnon et al., Nature Neuroscience, 2014]
Researchers at Kings College London used donated brain tissue to validate the discovery of a new cell signalling pathway involved in Alzheimer’s disease. They identified a series of protein interactions that can contribute to the damage of brain cells and showed this pathway is activated in the brains of people with Alzheimer’s disease but not other forms of dementia. Scientists will now work to develop drugs that can interfere with this pathway and hopefully prevent the disease from progressing.
[Clusterin regulates b-amyloid toxicity via Dickkopf-1-driven induction of the wnt–PCP–JNK pathway. R Killick et al., Molecular Psychiatry, 2014]
A global research team, led by scientists from University College London, unravelled more of the genetics of Alzheimer’s disease when they discovered a rare gene change linked to a higher risk of Alzheimer’s. The team studied the DNA code of people with and without Alzheimer’s disease and linked rare changes in a gene called TREM2 to a three-fold higher risk of the disease. The researchers used brain tissue to look for the presence of the altered gene in people with Alzheimer’s. The TREM2 gene plays a role in inflammation, highlighting it as an important process in the disease and opening the door to an exciting new area of research. The findings are helping to shape our understanding of the disease, as well as highlighting possible new targets for treatments.
[TREM2 variants in Alzheimer’s disease. R Guerreiro et al., New England Journal of Medicine, 2013]
Brain samples donated to the brain banks in Manchester and Newcastle, which both benefit from BDR support, were used to investigate genetic risk factors for dementia with Lewy bodies (DLB). The study was a joint effort by more than 50 researchers from all across the world, who pooled expertise to study the role of a gene called GBA1 in the disease. Subtle changes in the gene had already been linked to a higher risk of Parkinson’s disease and with the help of donated brain tissue, the team found that similar changes in the GBA1 gene were also associated with higher risk of DLB. The study is helping scientists to pinpoint the biological mechanisms involved in DLB, paving the way for research into new treatments.
[A multicentre study of glucocerebrosidase mutations in dementia with Lewy bodies. MA Nalls et al., JAMA Neurology, 2013]
Manchester scientists have used donated brain tissue to help improve the accuracy of dementia diagnosis. They studied the history of 228 patients that had been diagnosed with different forms of early-onset dementia using a combination of diagnostic methods and clinical observations. The team wanted to see whether the diagnosis given during life matched with the disease that was evident in the brain after death. They found that, despite a small number of discrepancies, the majority of cases were correctly diagnosed, supporting the use of these diagnostic methods to help people get the right diagnosis.
[The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships. JS Snowden et al., Brain, 2012]
Scientists at the Institute for Ageing and Health at Newcastle University gained a greater understanding of the risk factors for dementia in stroke survivors. They followed 355 participants who had strokes, comparing their memory and thinking skills during life with changes in their brain after death. The researchers found a higher risk of dementia in stroke-survivors that also had three or more other vascular risk factors. The findings suggest that treatment and monitoring of these risk factors may help prevent dementia in people who have had a stroke.
[Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. L Allan et al., Brain, 2011]