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O4‐03‐06: Familial Als‐associated Fused in Sarcoma (fus) Mutations Disrupt Transportin‐mediated Nuclear Import
Author(s) -
Haass Christian,
Rodde Ramona,
Edbauer Dieter,
Bentmann Eva,
Fischer Ingeborg,
Hruscha Alexander,
Than Manuel,
Mackenzie Ian,
Capell Anja,
Schmid Bettina,
Neumann Manuela,
Dormann Dorothee
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.08.051
Subject(s) - nuclear transport , frontotemporal lobar degeneration , nuclear localization sequence , nls , stress granule , biology , amyotrophic lateral sclerosis , nuclear export signal , neurodegeneration , pathogenesis , cytoplasm , microbiology and biotechnology , cell nucleus , genetics , pathology , medicine , gene , frontotemporal dementia , disease , immunology , dementia , translation (biology) , messenger rna
Background: Amyloid-b (Ab) aggregates are presumed to be found in the brain at an early stage of Alzheimer’s disease (AD) but have seldom been assessed by brain biopsy during life. The aim of this study was to analyze whether Ab and/or HPt in frontal cortical biopsies, obtained during evaluation of suspected normal pressure hydrocephalus (NPH), would predict later development of clinical AD. Methods: Between 1991 and 2006, we had evaluated 468 patients with suspected NPH with intraventricular pressure monitoring and a right frontal cortical biopsy sample immunostained for Ab and HPt. Adequate samples and the clinical follow-up data until death or the end of 2008, available in 433 cases, were reviewed for the clinical signs of dementia, including AD. Logistic regression analysis was used to analyze whether Ab and/or HPt in the biopsy samples obtained during life predicted development of clinical AD. Results: Of the 433 frontal cortical samples, 42 (10%) displayed both Ab and HPt, 144 (33%) Ab only, and 247 (57%) neither Ab nor HPt. In a median follow-up time of 4.4 years, 94 patients (22%) had developed clinical AD. The presence of both Ab and HPt associated strongly (odds ratio [OR], 72.5; 95% confidence interval [CI], 23.7-222) and Ab alone significantly (OR, 11.2; 95% CI, 5.1-24.7) with the clinical diagnosis of AD. Conclusions: (1) The presence of Ab and HPt in frontal cortical brain biopsy sample spoke strongly for the presence or later development of clinical AD, (2) Ab alonewas suggestive of AD, and (3) the absence of Ab and HPt spoke against later clinical diagnosis of AD. In conclusion, our results support the concept of preclinical AD and use of brain biopsy when available for validation of non-invasive diagnostic methods.