Alzheimer's Disease

Project Details

The key pathological hallmarks of AD are the extracellular amyloid plaques and the intracellular tangles. The principle component of plaques is the amyloid beta peptide (Aβ). The Aβ peptide is derived from the proteolytic cleavage of the amyloid precursor protein (APP). The Aβ peptide is believed to provide the neurotoxic insult that causes the neurodegeneration that leads to AD.

Structure – function studies of the APP-family

The normal function of APP and the amyloid precursor-like proteins (APLP1 and APLP2) is unknown. The current data suggests they have a role in modulating cellular viability, since reducing the redundancy of the APP-gene family in APP-family double and triple knockout mice can lead to a lethal phenotype. Current studies are using APP-family knockout mice for in vitro cell based assays and in vivo whole animal studies to determine how APP-family expression affects cellular functions. 


Complementing the functional work is a structural project to understand the three dimensional structure of the APP molecule either alone or in co-complex with APP-binding proteins. Knowing the structure of APP will provide insights into APP function. The structures will identify targets upon which to develop drugs to modulate APP processing and therefore prevent Aβ generation.

Mechanisms of amyloid toxicity

The cellular and molecular factors mediating Aβ neurotoxicity remain poorly defined. Cell culture models are being used to identify the molecular targets of Aβ as well as the cellular and subcellular changes that occur following exposure to toxic Aβ. These studies will identify the neurotoxic Aβ species, Aβ receptors and markers of Aβ toxicity. These factors become targets that can be inhibited to prevent neurotoxicity. As well as developing imaging agents to detect the toxic species in AD subjects.

Research Group

Cappai Laboratory: Alzheimer's Disease, Prion Disease, Parkinson's Disease and Traumatic Brain Injury



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Pathology