TAILIEUCHUNG - Báo cáo khoa học: Amyloid-b protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice

Here we report on the role of Glu59 in the fumarate-mediated allosteric regulation of the human mitochondrial NAD(P) + -dependent malic enzyme (m-NAD-ME). In the present study, Glu59 was substituted by Asp, Gln or Leu. Our kinetic data strongly indicated that the charge properties of this residue significantly affect the allosteric activation of the enzyme. | ỊFEBS Journal Amyloid-b protofibril levels correlate with spatial learning in Arctic Alzheimer s disease transgenic mice Anna Lord1 Hillevi Englund1 Linda Soderberg2 Stina Tucker2 Fredrik Clausen3 Lars Hillered3 Marcia Gordon4 Dave Morgan4 Lars Lannfelt1 Frida E. Pettersson1 and Lars N. G. Nilsson1 1 Department of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Sweden 2 BioArctic Neuroscience AB Stockholm Sweden 3 Department of Neuroscience Neurosurgery Uppsala University Hospital Sweden 4 Department of Molecular Pharmacology and Physiology Alzheimer s Research Laboratory College of Medicine University of South Florida Tampa FL USA Keywords Alzheimer s disease amyloid-b protofibrils Arctic mutation spatiallearning transgenic mice Correspondence L. Nilsson Department of Public Health and Caring Sciences Molecular Geriatrics Uppsala University Rudbeck Laboratory Dag Hammarskjolds vag 20 751 85 Uppsala Sweden Fax 46 18 471 4808 Tel 46 18 471 5039 E-mail Received 29 August 2008 revised 23 October 2008 accepted 4 December 2008 doi Oligomeric assemblies of amyloid-b Ab are suggested to be central in the pathogenesis of Alzheimer s disease because levels of soluble Ab correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover such Ab species have been shown to be neurotoxic to interfere with learned behavior and to inhibit the maintenance of hippocampal long-term potentiation. The tg-ArcSwe model . transgenic mice with the Arctic and Swedish Alzheimer mutations expresses elevated levels of Ab protofibrils in the brain making tg-ArcSwe a highly suitable model for investigating the pathogenic role of these Ab assemblies. In the present study we estimated Ab protofibril levels in the brain and cerebrospinal fluid of tg-ArcSwe mice and also assessed their role with respect to cognitive functions. Protofibril levels specifically measured with a .

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