Amyloid imaging in Alzheimer’s disease and mild cognitive impairment by positron emission tomography

Effectiveness of future treatment strategies in Alzheimer s disease (AD) will rely on early detection of disease and the possibility to clearly evaluate their effects. The findings presented in this thesis concerns both early in vivo detection of amyloid deposition in the brains of patients at risk of developing AD and the longitudinal changes of pathological and functional parameters in patients with AD.

A couple of years ago the first study with in vivo detection of amyloid using the radiotracer N-methyl [11C] 2-(4´-methylaminophenyl)-6-hydroxy-benzothiazole also known as 11C-Pittsburgh Compound B (11C-PIB) with positron emission tomography (PET) was performed in collaboration between researchers in Pittsburgh, USA, Uppsala and Stockholm, Sweden. This first study showed a significant difference between AD patients and healthy controls in regards to their 11C-PIB retention. The research presented in this thesis is both continuations and new investigations based on this initial research.

Results obtained in the studies presented in this thesis showed that the amyloid deposition is an early event in the development of AD present already in patients with mild cognitive impairment (MCI) that later develop AD. We could also show that the amyloid deposition in brain was closely correlated to concentrations of pathological biomarkers in the cerebrospinal fluid (CSF) at an early stage. While functional decline with decreased cerebral metabolic rate of glucose (CMRglc) measured with 18F-FDG PET and episodic memory tests did not show a relationship in MCI patients but did at the clinical stage of AD. Our results also suggests that the early deposition of amyloid increase to a certain level and then reaches a plateau as shown by a quite stable 11C-PIB retention in AD patients followed for a mean period of 2.5 years. We could also show that the dynamic 11C-PIB PET scan do not only contain information on amyloid load but also information on brain function as the early frames contain a blood flow component that is related to CMRglc.

The general conclusions to be drawn from these studies are that 11C-PIB PET shows promising results of both early detection of disease and the possibility to use it for evaluation of current and future anti-amyloid therapies. The possibility to extract functional information will further increase the usefulness of 11C-PIB PET in AD research and clinical assessment of dementia.

List of scientific papers

I. Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, Wall A, Ringheim A, Långström B, Nordberg A (2006). Two-year follow-up of amyloid deposition in patients with Alzheimers disease. Brain. 129(Pt 11): 2856-66. Epub 2006 Jul 19.
https://pubmed.ncbi.nlm.nih.gov/16854944

II. Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, Ringheim A, Långström B, Nordberg A (2008). PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 29(10): 1456-65. Epub 2007 May 11.
https://pubmed.ncbi.nlm.nih.gov/17499392

III. Forsberg A, Engler H, Långström B, Nordberg A (2008). The use of PIB-PET as a pathological and functional marker in AD. [Submitted]

IV. Forsberg A, Almkvist O, Engler H, Wall A, Långström B, Nordberg A (2008). Amyloid deposition is an early event in AD showing complex relationships with CSF biomarkers and functional parameters. [Submitted]