Abstract Body

Aims

To use multimodal imaging to map important pathophysiological processes and delineate the outmost driving forces for the clinical phenotypes in Alzheimer´s disease (AD) and non-AD dementia.

Methods

We use a translational approach from multimodal tracer in vivo PET imaging to in vitro PET tracer binding in post-mortem brain tissue measuring amyloid, tau, astrogliosis and synapse loss.

Results

We observe a negative correlation between MAO-B inhibitor ¹¹C-deprenyl (astrogliosis) and ¹¹C-PIB (amyloid ) levels but a positive correlation between 11C-deprenyl and ¹⁸F-FDG (cerebral glucose metabolism) PET at early stages of preclinical /prodromal AD. This early sign of high astrogliosis may reflect an increase in neuroprotective astrocytic forms (A2) .In post-mortem AD brain an increased ³H-deprenyl binding positively correlates with amyloid load and probably represent the toxic astrocytic form (A1) although the astrocyte tracers deprenyl and BU99008 both show multiple binding sites in AD brain tissue. Deprenyl PET studies are for comparison ongoing in frontotemporal lobe dementia. Tau PET binding increases with progression of AD and show less correlation with PIB PET but negative correlation with FDG PET and cognition (episodic memory). Tau PET seems to better predict future cognitive decline than amyloid or FDG PET in AD. Characterization of the binding properties of the synapse protein tracer ³H-UCBJ is ongoing in post-mortem brain tissue to be continued by PET studies in early AD and non-AD dementia.

Conclusions

Multimodal PET tracer imaging will increase the precision of early diagnosis, clinical prognosis and development and assessment of outcome of new drug treatment strategies.