Identification and characterisation of phenotypic modifier genes in familial Alzheimer's disease [ 2004 - 2006 ]

Research Grant

Researchers: Prof Peter Schofield (Principal investigator) ,  A/Pr John Kwok ,  Dr William Brooks

Brief description Alzheimer's disease (AD) is the most common cause of dementia the fourth most common cause of death. There are no effective cures for AD and those drugs currently available are of very limited value in delaying the onset and progression of this invariably fatal disease. AD is diagnosed by two key features in the brain, dense plaques composed of the amyloid beta peptide, and tangles composed of the tau protein. The identification of new therapeutic targets, such as the enzymes which produce amyloid beta peptide, and the development of drugs that interact with these targets offers the prospect of developing treatments to delay disease onset, retard or even halt the development of this relentlessly progressive disease. Our research focuses on the genes that are involved in variant forms of AD. One neuropathological variant form we and others have described is characterised by large diffuse (cotton wool) amyloid plaques. Cotton wool plaque pathology is associated with AD causing mutations in the presenilin 1 (PS-1) gene. Another clinical AD variant that we have described is characterised by the presence of spastic paraparesis (SP). SP is associated with PS-1 mutations, but when present delays disease onset. We have identified two potential modifier genes which are likely to be directly involved in the production of cotton wool plaques or modifying the effect of PS-1 mutations and the occurence of SP. For both genes, the goal of this project is to use a range of genetic approaches to clone the modifier genes by and to assess their effects on the clinical and pathological development of AD. By studying the effects of genes which act to modify the effects of the PS-1 mutations in these variant forms of AD we hope to gain a greater understanding of how the plaques and tangles actually lead to the clinical symptoms of the disease and to gain insights into new ways in which AD may be treated.

Funding Amount $AUD 413,250.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant