A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease.

Abstract

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.

• Authors: Atsushi Ishikawa, Yue-Shan Piao, Akinori Miyashita, Ryozo Kuwano, Osamu Onodera, Hiroaki Ohtake, Masahiro Suzuki, Masatoyo Nishizawa, Hitoshi Takahashi
• Journal: Annals of neurology (Ann Neurol) Vol. 57 Issue 3 Pg. 429-34 (Mar 2005) ISSN: 0364-5134 [Print] United States
• PMID: 15732120 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Membrane Proteins
• Nerve Tissue Proteins
• PSEN1 protein, human
• Presenilin-1
• SNCA protein, human
• Synucleins
• alpha-Synuclein

Topics

• Alzheimer Disease (complications, genetics, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Brain (pathology)
• DNA Mutational Analysis (methods)
• Exons
• Humans
• Immunohistochemistry (methods)
• Lewy Body Disease (etiology, genetics, metabolism, pathology)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Mutation
• Nerve Tissue Proteins (metabolism)
• Neurologic Examination (methods)
• Plaque, Amyloid
• Presenilin-1
• Synucleins
• alpha-Synuclein