Genetic mosaicism is a condition where cells within the same individual have different genetic makeup. This can occur due to mutations that happen after fertilization, meaning that not all cells in the body carry the same genetic changes. In the context of dementia, particularly Alzheimer’s disease, genetic mosaicism has been gaining attention for its potential role in increasing the risk of developing this condition.
Alzheimer’s disease is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, leading to neuronal loss and cognitive decline. One of the most well-known genetic factors linked to Alzheimer’s is the presence of an extra copy of chromosome 21, which is associated with Down syndrome. Individuals with Down syndrome are at a high risk of developing Alzheimer’s due to the overexpression of the amyloid precursor protein (APP) gene located on chromosome 21[1].
Genetic mosaicism can affect the brain in various ways. For instance, some individuals with Down syndrome may exhibit mosaicism, where only a portion of their cells have the extra chromosome 21. Studies have shown mixed results regarding the impact of mosaicism on dementia risk in these individuals. Some research suggests that mosaicism might reduce the risk of dementia, while other studies indicate it could increase susceptibility to neurodegenerative conditions[1].
Beyond Down syndrome, genetic mosaicism in the brain itself can also contribute to Alzheimer’s disease. This type of mosaicism involves cells in the brain having different genetic mutations than other cells in the body. Such mutations can lead to the formation of clones of cells with altered functions, potentially contributing to neurodegeneration. For example, somatic mutations in microglia, a type of brain cell involved in immune responses, have been linked to inflammation and neuronal damage in Alzheimer’s disease[5].
The role of genetic mosaicism in dementia highlights the complexity of neurodegenerative diseases. It suggests that not only inherited genetic factors but also random mutations occurring during life can influence an individual’s risk of developing dementia. Understanding these mechanisms could lead to new therapeutic strategies targeting specific cellular pathways affected by genetic mosaicism.
In conclusion, genetic mosaicism plays a significant role in the risk of developing dementia, particularly Alzheimer’s disease. Further research into this area may uncover new avenues for prevention and treatment, offering hope for those affected by these devastating conditions.
