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Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome

This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS an...

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Autores principales: Salcedo-Arellano, Maria Jimena, Sanchez, Desiree, Wang, Jun Yi, McLennan, Yingratana A., Clark, Courtney Jessica, Juarez, Pablo, Schneider, Andrea, Tassone, Flora, Hagerman, Randi J., Martínez-Cerdeño, Verónica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485779/
https://www.ncbi.nlm.nih.gov/pubmed/34602969
http://dx.doi.org/10.3389/fnins.2021.720253
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author Salcedo-Arellano, Maria Jimena
Sanchez, Desiree
Wang, Jun Yi
McLennan, Yingratana A.
Clark, Courtney Jessica
Juarez, Pablo
Schneider, Andrea
Tassone, Flora
Hagerman, Randi J.
Martínez-Cerdeño, Verónica
author_facet Salcedo-Arellano, Maria Jimena
Sanchez, Desiree
Wang, Jun Yi
McLennan, Yingratana A.
Clark, Courtney Jessica
Juarez, Pablo
Schneider, Andrea
Tassone, Flora
Hagerman, Randi J.
Martínez-Cerdeño, Verónica
author_sort Salcedo-Arellano, Maria Jimena
collection PubMed
description This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS and Alzheimer's Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (−6.28%), globus pallidus (−10.95%), hippocampus (−6.95%), and amygdala (−7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid β plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities.
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spelling pubmed-84857792021-10-02 Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome Salcedo-Arellano, Maria Jimena Sanchez, Desiree Wang, Jun Yi McLennan, Yingratana A. Clark, Courtney Jessica Juarez, Pablo Schneider, Andrea Tassone, Flora Hagerman, Randi J. Martínez-Cerdeño, Verónica Front Neurosci Neuroscience This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS and Alzheimer's Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (−6.28%), globus pallidus (−10.95%), hippocampus (−6.95%), and amygdala (−7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid β plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities. Frontiers Media S.A. 2021-09-17 /pmc/articles/PMC8485779/ /pubmed/34602969 http://dx.doi.org/10.3389/fnins.2021.720253 Text en Copyright © 2021 Salcedo-Arellano, Sanchez, Wang, McLennan, Clark, Juarez, Schneider, Tassone, Hagerman and Martínez-Cerdeño. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Salcedo-Arellano, Maria Jimena
Sanchez, Desiree
Wang, Jun Yi
McLennan, Yingratana A.
Clark, Courtney Jessica
Juarez, Pablo
Schneider, Andrea
Tassone, Flora
Hagerman, Randi J.
Martínez-Cerdeño, Verónica
Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title_full Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title_fullStr Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title_full_unstemmed Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title_short Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
title_sort case report: coexistence of alzheimer-type neuropathology in fragile x-associated tremor ataxia syndrome
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485779/
https://www.ncbi.nlm.nih.gov/pubmed/34602969
http://dx.doi.org/10.3389/fnins.2021.720253
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