Microstructure of Brain Reserve Study

Project Outlines and Aims

The biological foundation for the Brain Reserve effect is unknown. This study will tackle this question by testing predictions based on three potential mediatory mechanisms: neuroprotection, neurogeneration or compensation.

Alzheimer disease (AD) burden and neuroplasticity (neurogenesis, neural density and synaptic density) measures in the hippocampus and Brodmann area 9 of individuals with high versus low mental activity will be compared. This is a world-first study made possible by access to the unique Cognitive Function & Ageing Study (CFAS) MRC brain bank based in the UK, in collaboration with the CFAS leaders. Importantly, a community-based sampling strategy has been employed to avoid the disease severity bias that is inherent in post mortem samples.

So far we have identified appropriate cases from the CFAS sample, tissue blocks and slides have been transported to Sydney and we have preliminary semi-quantitative CERAD-rated data of disease burden differences between the two mental activity groups. Stereological quantitation of these differences is ongoing, as is quantification of neuroplastic changes, which are likely to be the critical factor. This study may have important ramifications if it can reveal why a large proportion of individuals with high disease burden remain clinically unaffected – data which may even find pharmacological relevance.

Staff

Dr Michael Valenzuela (chief investigator)
Marshall Dalton (research assistant)
Professor Perminder Sachdev

Collaborators

Professor Carol Brayne, Cambridge University UK
Professor Paul Ince, Sheffield University UK
Dr Fiona Matthews, Cambridge University UK
Associate Professor Jillian Kril, University of Sydney
Professor Glenda Halliday, Prince of Wales Medical Research Institute