Update on Parkinson’s disease studies using brain tissue
Several interesting and diverse clinicopathological studies (where disease information is correlated with pathology) have been performed recently with the information available to us from our brain donors. One such study looked at the progression of pathology in patients with Parkinson’s disease (PD) and found that in most cases the progression is not rapid at all but rather it takes more than 13 years (on average) before a phase of the disease with a more rapid decline commences. Fewer than 10% of patients have a more rapid decline and future studies need to investigate these patients more closely to try and identify what it is that causes this and how these patients can be identified early in their disease course. Another study found that 83% of individuals with PD will develop some degree of dementia after 20 years. This may seem a rather depressing statistic, but in bringing awareness to the community it gives people with PD and their carers the opportunity to think ahead and prepare for what may happen in the future.
Studies examining the pathology alone of brain tissue have also provided some interesting insights into disease mechanisms. One region of the brain that is particularly targeted by abnormal protein deposits in Lewy body diseases (that is, PD, PD with dementia and dementia with Lewy bodies) is the intralaminar thalamus. This region contains several subregions, called nuclei, which were shown in a recent study to have specific patterns of cell and tissue loss and accumulations of Lewy bodies that relate to the severity of Lewy body pathology throughout the rest of the brain, aging and the presence of dementia and visual hallucinations.
DNA studies examining normal differences in genes that a certain percentage of the population has (known as polymorphisms) have found that polymorphisms in genes responsible for inherited PD can cause either an increased or decreased risk of developing PD, depending on which one of the gene is involved. Another polymorphism associated with a familial PD gene has been found to affect the age of onset of the disease.
Update on studies using brain tissue from other Parkinsonian disorders
Another subset of rarer movement disorders are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A project using tissue from donors with MSA has demonstrated that a protein present in Lewy bodies called LRRK2 was also present early in the formation of glial cytoplasmic inclusions (GCI), the pathological characteristic of MSA. LRRK2 may be an important factor in the disease as its expression increased with the amount of GCIs, myelin degradation and cell loss. PSP can be difficult to treat as it often exhibits an unsatisfactory response to levadopa therapy. More widespread loss of cells of the extranigral A10 region of the substantia nigra was recently discovered (compared to PD cases, who usually have an adequate response to levadopa), indicating that these cells may be required for a good response to levadopa therapy.
In trying to understand the yet unknown causes about why older people fall over, we looked at fatigue. It is an ideal candidate. Firstly, fatigue is a common complaint for older people; more than 50 percent of people aged 70+ report fatigue in their daily activities. Secondly, fatigue affects sensory and movement functions that are associated with falling, such as […]