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- W2339796242 abstract "Neuropathologic evaluation of dementia is aided by availability of specific antibodies detecting protein inclusions. There is greater awareness of the co-existence of proteinopathies in neurodegenerative disorders, some of which are defined as atypical dementias. We describe two cases studied at Indiana Alzheimer Disease Center and presenting challenges for classification. Post-mortem histology and immunohistochemistry were carried out and antibodies against tau, amyloid β (Aβ), α-synuclein and TDP-43 were used. For genetics, DNA was extracted from brain tissue and direct sequencing is in progress. At age, 50 and 53, respectively, two males (S1 and S2), presented with neurological symptoms. S1 had impairment of memory and executive functions. At age 54, he was diagnosed with Alzheimer disease; at 55, the diagnosis was revised as dementia with pronounced amnestic component. At age 62, frontotemporal dementia (FTD) was considered. He died at age 66. S2 presented depression, social withdrawal, apathy, and hyperphagia. At age 58, MRI showed atrophy of hippocampus, as well as frontal and parietal lobes. A diagnosis of semantic and behavioral FTD was made. Death occurred at age 61. At autopsy, the brains weighed 836 and 1,246 grams, respectively and showed atrophy in same anatomical regions. Atrophy of head of caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, temporal cortex, hippocampus and parahippocampal cortex was seen. The substantia nigra was severely depigmented. In S1, tau and Aβ load was severe in neocortex and hippocampus. TDP-43 inclusions were numerous in cytoplasm of neurons of neocortex, basal ganglia, pyramidal and granule cell layer of hippocampus and in neurites. Granule cells of fascia dentata were TDP-43 immunopositive. Hippocampal sclerosis was present. α-synuclein positive inclusions were seen in cingulate gyrus. In S2, tau-immunoreactive neurons, glia and neurites were severe in frontal cortex; glial involvement of subcortical white matter was severe. TDP-43 immunoreactive neuronal intracytoplasmic inclusions and neurites were numerous in frontal cortex and subcortical white matter. Complex protein interactions may lead to atypical clinical phenotypes that defy neurologic classification. Misfolded proteins with variable patterns of distribution result in complex combinations of system degeneration which require a detailed neuropathologic assessment." @default.
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- W2339796242 date "2015-07-01" @default.
- W2339796242 modified "2023-09-27" @default.
- W2339796242 title "P1-086: Multiple proteinopathies underlying atypical dementia" @default.
- W2339796242 doi "https://doi.org/10.1016/j.jalz.2015.06.283" @default.
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