A Second Pedigree with Amyloid-less Familial Alzheimer's Disease Harboring an Identical Mutation in the Amyloid Precursor Protein Gene (E693delta)

作者：Kutoku Yumiko; Ohsawa Yutaka; Kuwano Ryozo; Ikeuchi Takeshi; Inoue Haruhisa; Ataka Suzuka; Shimada Hiroyuki; Mori Hiroshi; Sunada Yoshihide^*

来源：Internal Medicine, 2015, 54(2): 205-208.

DOI：10.2169/internalmedicine.54.3021

• Alzheimer's disease
• familial Alzheimer's disease
• APP gene
• A beta oligomers
• PET

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 beta (A beta) 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 A beta-reactive bands was detected in the patient's CSF. Our findings suggest that soluble A beta-oligomers induce neuronal toxicity, independent of insoluble A beta fibrils.

• 出版日期2015