Peter Parbo and Rola Ismail, march 2016

Main supervisor: David J. Brooks, MD DSc FRCP FMedSci

Objectives

A total of 84,000 people in Denmark suffer from dementia. The prevalence of dementia is estimated to triple over the next 50 years. Alzheimer’s disease (AD) causes 70% of cases and is clinically characterised by progressive worsening of memory and other cognitive functions. At post-mortem its neuropathological hallmarks are extracellular deposits (plaques) of beta-amyloid peptides and intracellular neurofibrillary tangles of abnormally aggregated tau protein. These pathologies result in neuronal loss and are associated with local brain inflammation in the form of microglial activation. Positron emission tomography (PET) imaging allows us to detect the presence of beta-amyloid plaques, tau tangles and inflammation in vivo in the brain. Mild cognitive impairment (MCI) is a prodrome of dementia where subjects have memory problems but are still capable of independent living. Previous studies have found that 60% of MCI subjects have brain amyloid on imaging, providing evidence of prodromal AD, and 40% have accompanying brain inflammation.

Study description

At the Department of Nuclear Medicine & PET Centre in Aarhus we are currently studying the spatial and temporal relationships between these pathologies, using [11C]PiB (beta-amyloid), [18F]AV-1451 (tau) and [11C]PK11195 (inflammation) PET and aiming to clarify the role of brain inflammation in subjects at risk of developing Alzheimer’s disease. This may help rationalise the use of anti-inflammatory agents as neuroprotective strategies in MCI and AD.
The Lundbeck Foundation and the Danish Council for Independent Research are funding the research programme.

 

Figur 1: A series of beta-amyloid (PiB), tau (AV-1451) and inflammation (PK11195)  PET images of the brain of a subject with mild cognitive impairment. Upper row: [11C]PiB PET 60-90 min. SUVRcb (range 0-3.5); middle  row: [18F]AV-1451 PET 80-120 min. SUVRcb (range 0-2.5); lower  row: [11C]PK11195 SVCA6 BP (range 0-1). (SUVR=standardised uptake value ratio; cb=cerebellar cortex used as reference; SVCA6=supervised cluster analysis with 6-classes; BP=binding potential).