Association of PSEN1 Mutation with Dementia with Lewy Bodies without Features of Alzheimer’s Disease

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Tanesh Ayyalu, MD Jason Fredrick, MD Neeraj Singh, MD


Dementia with Lewy bodies affects 0.4% of people over the age of 65 each year, making it the second most common neurodegenerative form of dementia following Alzheimer’s disease. It is more commonly diagnosed over the age of 50, and in men more than in women. As a synucleinopathy, in which alpha-synuclein inclusions accumulate in neurons, dementia with Lewy bodies shares many clinical features with idiopathic Parkinson’s disease, including bradykinesia, visual hallucinations, and cognitive decline. Neuroimaging in dementia with Lewy bodies reveals occipital and parietal atrophy and hypometabolism. Some cases of dementia with Lewy bodies and idiopathic Parkinson’s disease have been shown to be associated with genetic mutations, such as in the GBA gene. In this case report, we present a unique case of a young man who started showing clinical features of dementia with Lewy bodies at the age of 43, with further confirmation of the diagnosis in neuroimaging studies. However, his genetic test results revealed the presence of a PSEN1 mutation, which has been described with Alzheimer’s disease, even though he did not show typical clinical or neuroimaging findings that matched with Alzheimer’s disease. This report reveals a potential unique association of the PSEN1 mutation with early-onset dementia with Lewy bodies, indicating that we may have an incomplete understanding of the function of such genes in cognitive development, as well as the phenotypic presentations of dementia with Lewy bodies, idiopathic Parkinson’s disease, and Alzheimer’s disease.

Keywords: PSEN1 Mutation, Dementia with Lewy Bodies, Alzheimer's Disease, Neuroimaging, Synucleinopathy, Genetic Mutations, Cognitive Decline, Early-Onset Dementia, Parkinson's Disease, Phenotypic Presentations

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AYYALU, Tanesh; FREDRICK, Jason; SINGH, Neeraj. Association of PSEN1 Mutation with Dementia with Lewy Bodies without Features of Alzheimer’s Disease. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <>. Date accessed: 22 july 2024. doi:
Case Reports


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