Alzheimer's

Overview

Using a functional genomics approach, I am evaluating candidate genes for Alzheimer’s disease (AD) to determine their role in disease susceptibility.

Candidate genes have been selected based on current genetic and functional data; genes under study include those involved in both production and degradation of the Aβ peptide. Bacterial artificial chromosomes (BACs) for each candidate gene can be modified at specific loci using DNA recombination to create BACs expressing specific gene variants. A newly developed method using Herpes Simplex Virus-1 (HSV-1) makes it possible to package each gene variant into virions. Following infection of suitable cells, clonal cell lines can be established for functional assessment.

Background

Alzheimer’s disease (AD) is the most common of the neurodegenerative disorders and dementia affects approximately 700,000 individuals in the UK.

AD is typically classified into two types; early onset (EO) and sporadic late onset (LO) forms. The study of rare families with EOAD led to the discovery of three genes that contained mutations which led to the development of AD. These are 1) amyloid precursor protein (APP), 2) presenilin-1 and 3) presenilin-2. Understanding the cause of the more common, greater than 99%, LO form of AD has proven far more challenging. At present, there is one well-replicated risk factor for LOAD, the epsilon;4 allele of the Apolipoprotein E (APOE) gene. However, 50% of the individuals who carry the epsilon;4 allele will not develop AD, and indeed the opposite is also true. APOE epsilon;4 is therefore a risk factor for AD rather than a causal gene.

Estimates suggest that 30-70% of the variance in AD can be explained by as yet unidentified genes. The identification of these risk genes is a priority in the field of AD research. Understanding more about the molecular processes underlying this devastating disease will facilitate the design of new therapeutics to slow disease progression and may ultimately lead to a cure.

	Introduction Projects Funding Collaborators Links Publications Contact	Alzheimer's Overview Using a functional genomics approach, I am evaluating candidate genes for Alzheimer’s disease (AD) to determine their role in disease susceptibility. Candidate genes have been selected based on current genetic and functional data; genes under study include those involved in both production and degradation of the Aβ peptide. Bacterial artificial chromosomes (BACs) for each candidate gene can be modified at specific loci using DNA recombination to create BACs expressing specific gene variants. A newly developed method using Herpes Simplex Virus-1 (HSV-1) makes it possible to package each gene variant into virions. Following infection of suitable cells, clonal cell lines can be established for functional assessment. Background Alzheimer’s disease (AD) is the most common of the neurodegenerative disorders and dementia affects approximately 700,000 individuals in the UK. AD is typically classified into two types; early onset (EO) and sporadic late onset (LO) forms. The study of rare families with EOAD led to the discovery of three genes that contained mutations which led to the development of AD. These are 1) amyloid precursor protein (APP), 2) presenilin-1 and 3) presenilin-2. Understanding the cause of the more common, greater than 99%, LO form of AD has proven far more challenging. At present, there is one well-replicated risk factor for LOAD, the epsilon;4 allele of the Apolipoprotein E (APOE) gene. However, 50% of the individuals who carry the epsilon;4 allele will not develop AD, and indeed the opposite is also true. APOE epsilon;4 is therefore a risk factor for AD rather than a causal gene. Estimates suggest that 30-70% of the variance in AD can be explained by as yet unidentified genes. The identification of these risk genes is a priority in the field of AD research. Understanding more about the molecular processes underlying this devastating disease will facilitate the design of new therapeutics to slow disease progression and may ultimately lead to a cure.
	Updated: Wed, 22nd September, 2010