A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease.
We report early-onset parkinsonism and dementia of 18 years' duration in a 52-year-old man whose grandfather and father had suffered from a similar neurological disease. In this patient, we found neuronal loss in various brain regions including the substantia nigra and cerebral cortex, Lewy bodies, cotton wool plaques, corticospinal tract degeneration, cerebral amyloid angiopathy, and a novel three-base pair deletion in exon 12 of the presenilin-1 (PSEN1) gene. We considered that the mutant PSEN1 might play an important role in the pathogenetic process of both aggregation of alpha-synuclein into Lewy bodies and deposition of beta-amyloid into cotton wool plaques.
Ishikawa
Atsushi
A
Department of Neurology, Nishi-Ojiya National Hospital, Ojiya, Japan. ishikawa@agano.ne.jp
Piao
Yue-Shan
YS
Miyashita
Akinori
A
Kuwano
Ryozo
R
Onodera
Osamu
O
Ohtake
Hiroaki
H
Suzuki
Masahiro
M
Nishizawa
Masatoyo
M
Takahashi
Hitoshi
H
D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020961:Lewy Body Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009460:Neurologic Examination / Q000379:methods; D058225:Plaque, Amyloid; D053764:Presenilin-1; D051843:Synucleins; D051844:alpha-Synuclein
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein