Biomarkers and novel therapies for dementia

Kristoffer Haugarvoll, MD, PhD is Principal Investigator (PI) in the Bergen Dementia Research Group and Consultant Neurologist at the Department of Neurology, Haukeland University Hospital. Dr. Haugarvoll’s clinical expertise includes neurodegeneration, movement disorders, dementia, and neurogenetics. His main research focus is dementia and neurodegeneration in particular dementia related to the Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and the Parkinson’s disease dementia (PDD) spectrum.

The group aims at identifying novel biomarkers for dementia and stratifying dementias according to underlying molecular patterns. In 2021, they will start a new cohort study – STRAT-COG. This study aims to establish a comprehensive biomarker panel for dementia by combining existing biomarkes for Alzheimer’s pathology with biomarkers for neuronal loss and α-synuclein pathology. This will enable the group to elucidate how the mixture of different molecular pathologies affects prognosis, and to stratify individual patients suffering from dementia based on underlying biological processes. STRAT-COG will include a brain donation program.

In 2020, the Bergen Dementia Research Group started recruiting individuals with mild cognitive impairment to the ongoing Dementia Disease Initiation (DDI) project (PI: Tormod Fladby).

The Bergen Dementia Research Group is a partner in the ANeED study: Ambroxol in New and Early Dementia with Lewy Bodies (PI: Arvid Rongve). The ANeED study is a national multicentre phase III RCT clinical intervention study with Ambroxol in prodromal and mild DLB in Memory Clinics in Norway. Patient inclusion will start in 2021.

Selected Key Publications

1. Gaare JJ, Nido G, Dölle C, Sztromwasser P, Alves G, Tysnes OB, Haugarvoll K, Tzoulis C. Meta-analysis of whole-exome sequencing data from two independent cohorts finds no evidence for rare variant enrichment in Parkinson disease associated loci. PLoS One. 2020 Oct 1;15(10):e0239824. PMID: 33002040
2. Nido GS, Dick F, Toker L, Petersen K, Alves G, Tysnes OB, Jonassen I, Haugarvoll K, Tzoulis C Common gene expression signatures in Parkinson’s disease are driven by changes in cell composition. Acta Neuropathol Commun. 2020 Apr 21;8(1):55. PMID: 32317022
3. Gaare JJ, Nido GS, Sztromwasser P, Knappskog PM, Dahl O, Lund‐Johansen M, MD, Maple‐Grødem J, Alves G, Tysnes OB, Stefan Johansson S, Haugarvoll K, Tzoulis C. Rare genetic variation in mitochondrial pathways influences the risk for Parkinson’s disease. Mov Disord. 2018 Oct;33(10):1591-1600. PMID: 30256453.
4. Flønes IH, Fernandez-Vizarra E, Lykouri M, Brakedal B, Skeie GO, Miletic H, Lilleng PK, Alves G, Tysnes OB, Haugarvoll K, Dölle C, Zeviani M, Tzoulis C. Neuronal complex I deficiency occurs throughout the Parkinson’s disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage. Acta Neuropathol. 2018 Mar;135(3):409-425. PMID: 29270838
5. Nido GS, Dölle C, Flønes I, Tuppen HA, Alves G, Tysnes OB, Haugarvoll K, Tzoulis C. Ultradeep mapping of neuronal mitochondrial deletions in Parkinson’s disease. Neurobiol Aging. 2018 Mar;63:120-127. PMID: 29257976
6. Brakedal B, Flønes I, Reiter SF, Torkildsen Ø, Dölle C, Assmus J, Haugarvoll K*, Tzoulis C*. Glitazone use associated with reduced risk of Parkinson’s disease. Mov Disord. 2017 Sep 1. doi: 10.1002/mds.27128. PMID: 28861893 *) Equal contribution.
7. Haugarvoll K, Johansson S, Rodriguez CE, Boman H, Haukanes BI, Bruland O, Roque F, Jonassen I, Blomqvist M, Telstad W, Månsson JE, Knappskog PM, Bindoff LA. GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies. PLoS One. 2017 Jan 4;12(1):e0169309. doi: 10.1371/journal.pone.0169309. PMID: 28052128
8. Brakedal B, Haugarvoll K*, Tzoulis C*. Simvastatin is associated with decreased risk of Parkinson disease. Ann Neurol. 2017 Feb;81(2):329-330. doi: 10.1002/ana.24857. PMID: 28019662 *) Equal contribution.
9. Dölle C, Flønes I, Nido GS, Miletic H, Osuagwu N, Kristoffersen S, Lilleng PK, Larsen JP, Tysnes OB, Haugarvoll K, Bindoff LA, Tzoulis C. Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease.Nat Commun. 2016 Nov 22;7:13548. doi: 10.1038/ncomms13548. PMID: 27874000
10. Tzoulis C, Schwarzlmüller T, Biermann M, Haugarvoll K, Bindoff LA. Mitochondrial DNA homeostasis is essential for nigrostriatal integrity. Mitochondrion. 2016 May;28:33-7. doi: 10.1016/j.mito.2016.03.003. PMID: 26979109
11. Haugarvoll K, Bindoff LA, Tzoulis C. Nigrostriatal denervation sine parkinsonism. Brain. 2016 Apr;139(Pt 4):e25. doi: 10.1093/brain/awv410. PMID: 26811251
12. Tzoulis C, Zayats T, Knappskog PM, Müller B, Larsen JP, Tysnes OB, Bindoff LA, Johansson S, Haugarvoll K. HTRA2 p.G399S in Parkinson disease, essential tremor, and tremulous cervical dystonia.Proc Natl Acad Sci U S A. 2015 Mar 30. pii: 201503105. PMID: 25825781