Alzheimer Disease: Deecke L

Walla P, Püregger E, Lehrner J, Mayer D, Deecke L, Dal Bianco P. · Department of Clinical Neurology, University Hospital, Medical University Vienna, Austria. · J Neural Transm. · Pubmed #15480853 No free full text.

Abstract: Effects related to depth of verbal information processing were investigated in probable Alzheimer's disease patients (AD) and age matched controls. During word encoding sessions 10 patients and 10 controls had either to decide whether the letter "s" appeared in visually presented words (alphabetical decision, shallow encoding), or whether the meaning of each presented word was animate or inanimate (lexical decision, deep encoding). These encoding sessions were followed by test sessions during which all previously encoded words were presented again together with the same number of new words. The task was then to discriminate between repeated and new words. Magnetic field changes related to brain activity were recorded with a whole cortex MEG.5 probable AD patients showed recognition performances above chance level related to both depths of information processing. Those patients and 5 age matched controls were then further analysed. Recognition performance was poorer in probable AD patients compared to controls for both levels of processing. However, in both groups deep encoding led to a higher recognition performance than shallow encoding. We therefore conclude that the performance reduction in the patient group was independent of depth of processing. Reaction times related to false alarms differed between patients and controls after deep encoding which perhaps could already be used for supporting an early diagnosis.The analysis of the physiological data revealed significant differences between correctly recognised repetitions and correctly classified new words (old/new-effect) in the control group which were missing in the patient group after deep encoding. The lack of such an effect in the patient group is interpreted as being due to the respective neuropathology related to probable AD. The present results demonstrate that magnetic field recordings represent a useful tool to physiologically distinguish between probable AD and age matched controls.

Baran H, Jellinger K, Deecke L. · Ludwig Boltzmann Institute of Clinical Neurobiology, Psychiatric Hospital Vienna, Austria. · J Neural Transm. · Pubmed #10226937 No free full text.

Abstract: L-kynurenine (L-KYN) serves as a substrate for the synthesis of neurotoxic 3-OH-kynurenine (3-OH-KYN) and neuroprotective kynurenic acid (KYNA). KYNA is able to interact with ionotropic excitatory amino acid receptors that are involved in a variety of neurodegenerative disorders. The purpose of the present study was to investigate the biosynthetic machinery of KYNA in several regions of Alzheimer's disease (AD) brain. The endogenous levels of L-KYN, 3-OH-KYN and KYNA in frontal cortex, caudate nucleus, putamen, hippocampus, and cerebellum of 11 autopsy confirmed cases of AD and 13 age-matched controls were analyzed. Subsequently, the activity of two proteins responsible for the production of KYNA, kynurenine aminotransferases I and II (KAT I and KAT II), was investigated. There was a trend for a decrease of L-KYN and 3-OH-KYN in all examined regions of AD brain, as compared to controls. However, KYNA was increased significantly in the putamen and caudate nucleus of AD, by 192 and 177%, respectively. In other areas of AD brain only a minor increase of KYNA was present. Elevated KYNA in the caudate nucleus and putamen correlated with a significant increase of KAT I activities in both nuclei-157 and 147%, respectively. A minor increase of KAT II was measured only in the caudate nucleus of AD subjects. Kinetic analysis of KAT I and II performed in the caudate nucleus of AD patients revealed a marked increase of Vmax, by 207 and 274% of controls, respectively. Km value for L-KYN using pyruvate as amino acceptor was significantly higher for KAT II (247% of controls). The present data indicate an elevated kynurenine metabolism in AD brain. A marked increase of KYNA in the caudate nucleus and putamen may compensate the hyperactivity of the striato-frontal loop in AD brains. Blockade of NMDA receptors by KYNA may be responsible for impaired memory, learning and cognition in AD patients.