A second pedigree with amyloid-less familial Alzheimer's disease harboring an identical mutation in the amyloid precursor protein gene (E693delta).
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.
Department of Neurology, Kawasaki Medical School, Japan.
Yumiko
Y
Kutoku
Yutaka
Y
Ohsawa
Ryozo
R
Kuwano
Takeshi
T
Ikeuchi
Haruhisa
H
Inoue
Suzuka
S
Ataka
Hiroyuki
H
Shimada
Hiroshi
H
Mori
Yoshihide
Y
Sunada
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography
C545487:APP protein, human; D000682:Amyloid; D016564:Amyloid beta-Protein Precursor