Partner 6: Karolinska Institutet [KI], Stockholm , Sweden

Scientist responsible: Dr Jin-Jing Pei

Brief description of our organization

At the Alzheimer’s Disease Research Center at Karolinska Institutet (KI-ADRC) we investigate the mechanisms behind Alzheimer’s disease (AD) from different perspectives, emphasizing the integration of basic neuroscience research with clinical research, molecular genetics, and epidemiology. We study the generation of beta-amyloid and its relation with other pathological markers of the disease, the mechanisms of genetic and environmental risk factors for AD, the relationship between altered tau protein and the progression of neurofibrillary changes and the characterization of genes associated with AD. We aim to contribute to the understanding of the cellular, metabolic, and molecular changes that induce AD pathology and help define new biomarkers and therapeutic markers for the disease.

The original publications before NAD

Pei J-J,  Sersen E, Iqbal K, Grundke-Iqbal I. Expression of Protein Phosphatases PP1, PP2A, PP2B, and PTP-1B and Protein kinases MAP Kinase and CDC2 in the Hippocampus of Patients with Alzheimer disease and Normal Aged Individuals. Brain Research 655 (1994):70-76.
Pei J-J,  Tanaka T, Tung Y-C, Braak E, Iqbal K, Grundke-Iqbal I. Glycogen synthase kinase-3: Distribution, Levels and Activity of Glycogen Synthase Kinase-3 in the Alzheimer Disease Brain. Journal of Neuropathology and Experimental Neurology 56 (1997): 70-78.
Pei J-J**, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Distribution of active glycogen synthase kinase 3b (GSK-3b) in brains staged for Alzheimer’s disease neurofibrillary changes. Journal of Neuropathology and Experimental Neurology 58 (1999): 1010-1019.
Pei J-J**, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Distribution of active forms of C-jun kinase (JNK) and p38 kinase in brains staged with Alzheimer’s disease neurofibrillary changes. Journal of Alzheimer’s Disease 3 (2001): 41-48.
Pei J-J**, Braak H, An W-L, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Up-regulation of mitogen activated protein kinase kinase and mitogen activated protein kinase is associated with the progression of Alzheimer’s disease neurofibrillary degeneration. Molecular Brain Res. 109/1-2 (2002): 45-53.
Pei J-J**, Braak H, Gong C-X, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Up-regulation of cell division cycle (cdc2) in neurons with early stage Alzheimer’s disease neurofibrillary changes. Acta Neuropathologica 104 (2002): 369-376.
Pei J-J**, Gong C-X, An W-L, Winblad B, Cowburn RF, Grundke-Iqbal I, Iqbal K. Okadaic acid-induced inhibition of protein phosphatase 2A produces activation of mitogen-activated protein kinases ERK1/2, MEK1/2 and p70 S6 similar to that in Alzheimer’s disease. American Journal of Pathology 163 (2003): 845-58.
Pei J-J**, Khatoon S, An W-L, Nordlinder M, Tanaka T, Braak H, Tsujio I, Takeda M, Alafuzoff I, Winblad B, Cowburn RF, Grundke-Iqbal I, Iqbal K. Role of protein kinase B in Alzheimer's neurofibrillary degeneration. Acta Neuropathologica 105 (2003): 381-392.
An W-L, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Grundke-Iqbal I, Winblad B, Pei J-J**. Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer’s disease. American Journal of Pathology 163 (2003): 591-607.
An W-L, Bjorkdahl C, Liu R, Cowburn RF, Winblad B, Pei J-J**. Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3b in SH-SY5Y neuroblastoma cells. J Neurochem 92 (2005): 1104-1115.
Liu R, Pei J-J, Wang X-C, Zhou X-W, Tian Q, Winblad B, Wang J-Z. Anoxia induces tau dephosphorylation through protein phosphatase-2A activation in rat brain slices. J Neurochem 94 (2005) 1225-34.
Li X, Alafuzoff I, Soininen H, Winblad B, Pei J-J**. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer’s disease brain. FEBS Journal 272 (2005): 4211-20.
Pei J-J**, An W-L, Zhou X-W, Nishimura T, Norberg J, Benedikz E, Götz J, Winblad B. P70 S6 kinase mediates tau phosphorylation and synthesis. FEBS Lett. 580 (2006):107-14.
Zhou XW, Li X , Bjorkdahl C, Sjogren MJ,  Alafuzoff I, Soininen H, Grundke-Iqbal I, Iqbal K, Winblad B, Pei J-J**. Assessments of the accumulation severities of amyloid ß-protein and hyperphosphorylated tau in the medial temporal cortex of control and Alzheimer's brains. Neurobiol Dis 22 (2006): 657-68.
Zhou X-W, Tanila H, Pei J-J**. Parallel increase in p70 kinase activation and tau phosphorylation (S262) with Aß overproduction. FEBS Lett 582 (2008):159-164.
Liu R, Zhou X-W, Tanila H, Bjorkdahl C, Wang J-Z, Guan Z-Z, Gustafsson J-Å, Winblad B, Pei J-J**. Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology. J Cell Mol Med 12 (2008):241-57.
Liu R, Zeng J, Zhou X , Pei JJ, Wang JZ. Frontiers of Medicine in China. 2008 (2):235-238.
Zhou X-W, Tanila H, Pei J-J**. Tau phosphorylation correlates with reduced methylation of protein phosphatases 2A. Neurobiol Dis 2008 31(3):386-94.

Link

http://ki.se/ki/jsp/polopoly.jsp?d=5528