A second pedigree with amyloid-less familial Alzheimer's disease harboring an identical mutation in the amyloid precursor protein gene (E693delta)

Internal Medicine
Yumiko KutokuYoshihide Sunada

Abstract

A 59-year-old woman developed early-onset, slowly progressive dementia and spastic paraplegia. positron emission tomography (PET) imaging revealed a large reduction in the level of glucose uptake without amyloid deposition in the cerebral cortex. We identified a homozygous microdeletion within the amyloid β (Aβ) coding sequence in the amyloid precursor protein (APP) gene (c.2080_2082delGAA, p.E693del) in three affected siblings and a heterozygous microdeletion in an unaffected sibling. The identical mutation was previously reported in the first Alzheimer's pedigree without amyloid deposits. Furthermore, an increase in high-molecular-weight Aβ-reactive bands was detected in the patient's CSF. Our findings suggest that soluble Aβ-oligomers induce neuronal toxicity, independent of insoluble Aβ fibrils.

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Citations

Oct 27, 2015·Journal of Cellular Physiology·Hany MareiThomas Caceci
May 31, 2018·Journal of Alzheimer's Disease : JAD·Erika N ClineWilliam L Klein
Apr 26, 2019·Annals of Clinical and Translational Neurology·Jacquelyn E BragginSuman Jayadev
Feb 26, 2020·International Journal of Molecular Sciences·Takami Tomiyama, Hiroyuki Shimada

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