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Early-Onset Familial Alzheimer's Disease (EOFAD)

Published online by Cambridge University Press:  02 December 2014

Liyong Wu
Affiliation:
McGill Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University Translational Neuroimaging Laboratory, Douglas Research Institute, McGill University Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China
Pedro Rosa-Neto
Affiliation:
McGill Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University Translational Neuroimaging Laboratory, Douglas Research Institute, McGill University McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, QC
Ging-Yuek R. Hsiung
Affiliation:
Division of Neurology, University of British Columbia, Vancouver, BC
A. Dessa Sadovnick
Affiliation:
Division of Neurology, University of British Columbia, Vancouver, BC Faculty of Medicine, Department of Medical Genetics, University of British Columbia, Vancouver, BC
Mario Masellis
Affiliation:
Department of Medicine (Neurology), Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada Brain Sciences Research Program, Sunnybrook Health Sciences Centre, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
Sandra E. Black
Affiliation:
Department of Medicine (Neurology), Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
Jianping Jia
Affiliation:
Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China
Serge Gauthier*
Affiliation:
McGill Centre for Studies in Aging (MCSA), Douglas Research Institute, McGill University
*
McGill Centre for Studies in Aging (MCSA), McGill University, 6825, Boul. LaSalle Blvd., Montreal, QC, H4H 1R3, Canada. Email: serge.gauthier@mcgill.ca
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Abstract

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Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2012

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