Correlating Familial Alzheimer's Disease Gene Mutations with Clinical Phenotype

Abstract

Alzheimer's disease (AD) causes devastating cognitive impairment and an intense research effort is currently devoted to developing improved treatments for it. A minority of cases occur at a particularly young age and are caused by autosomal dominantly inherited genetic mutations. Although rare, familial AD provides unique opportunities to gain insights into the cascade of pathological events and how they relate to clinical manifestations. The phenotype of familial AD is highly variable and, although it shares many clinical features with sporadic AD, it also possesses important differences. Exploring the genetic and pathological basis of this phenotypic heterogeneity can illuminate aspects of the underlying disease mechanism, and is likely to inform our understanding and treatment of AD in the future.

KEYWORDS::

• amyloid precursor protein
• dominantly inherited Alzheimer's disease
• early-onset dementia
• familial Alzheimer's disease
• presenilins

Financial & competing interests disclosure

This work was undertaken at University College London and University College London Hospitals, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an Alzheimer's Research Trust Coordination Centre. N Ryan is supported by a Clinical Research Training Fellowship from the Medical Research Council (UK). M Rossor is a site PI for the NIA-funded DIAN study, which receives additional support from DeNDRON, the NIHR clinical research network for dementia and neurodegenerative diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was undertaken at University College London and University College London Hospitals, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an Alzheimer's Research Trust Coordination Centre. N Ryan is supported by a Clinical Research Training Fellowship from the Medical Research Council (UK). M Rossor is a site PI for the NIA-funded DIAN study, which receives additional support from DeNDRON, the NIHR clinical research network for dementia and neurodegenerative diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.