Thesis defense KIm Bruggink (Donders series 216)
25 April 2016
Promotor: prof. dr. M.Willemsen, copromotors: dr. ir. M. Verbeek, dr. H.B. Kuiperij
Amyloid-beta and amyloid associated proteins in the pathogenesis and diagnosis of Alzheimer's Disease
The main pathological event in Alzheimer’s disease is cerebral deposition of the amyloïd-beta (Aβ) protein. Alzheimer can be diagnosed by measurements of certain forms of Aβ in cerebrospinal fluid. These tests however, are not well equipped to set a diagnosis in early disease stages. In addition, the distinction between Alzheimer’s disease and other forms of dementia can be challenging.
This study describes novel methods to diagnose Alzheimer by measurement of certain proteins in cerebrospinal fluid (CSF). Tests were designed to measure aggregates and a longer than normal variant of Aβ. Measurements of CSF samples from demented and non-demented persons demonstrated that small aggregates are not elevated in the CSF of Alzheimer patients. The longer Aβ isoform was found to be lower in Alzheimer patients than in controls.
In addition, I studied Aβ-associated proteins, which might also have potential as Alzheimer biomarkers. One of these complexes was more abundant in brain tissue from Alzheimer patients than controls. However, the current tests are potentially not sufficiently sensitive to detect low levels of the complexes in CSF.
Finally, in this study the discovery of a novel potential amyloid associated protein is described, that can bind Aβ in CSF and was demonstrated near Aβ deposits in the brain.