Alzheimer Disease: Jellinger K

Ransmayr G, Katzenschlager R, Dal-Bianco P, Wenning G, Bancher C, Jellinger K, Schmidt R, Poewe W. · Neurologische Universitätsklinik Graz, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #17640492 No free full text.

Abstract: Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis. We also guide in the management of DLB as pharmacological treatment can pose difficult dilemmas for the treating clinician.

Schmidt R, Kienbacher E, Benke T, Dal-Bianco P, Delazer M, Ladurner G, Jellinger K, Marksteiner J, Ransmayr G, Schmidt H, Stögmann E, Friedrich J, Wehringer C. · Univ.-Klinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18381051 No free full text.

Abstract: The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.

Ransmayr G, Wenning GK, Seppi K, Jellinger K, Poewe W. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020 Innsbruck. · Nervenarzt. · Pubmed #11139988 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, parkinsonian syndrome, fluctuations of cognitive functions, alertness, and attention, visual hallucinations (usually detailed and well described), depression, REM sleep behavior disorder, adverse responses to standard neuroleptics doses, falls, syncopes, systematized delusions, and other modalities of hallucinations. Specificity of the clinical diagnostic criteria is high (95%), and sensitivity is considerably lower. Mean age at disease onset ranges between 60 and 68 years. The male gender prevails. Disease duration is 6 to 8 years. The differential diagnoses of DLB are dementia of the Alzheimer type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and rarely Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. Controlled pharmacological studies have so far not been published. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha receptor-blocking medications to improve neurogenic bladder dysfunction.

Blasko I, Jungwirth S, Jellinger K, Kemmler G, Krampla W, Weissgram S, Wichart I, Tragl KH, Hinterhuber H, Fischer P. · Department of Psychiatry, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. · J Psychiatr Res. · Pubmed #18155247 No free full text.

Abstract: In the course of cognitive deterioration leading to Alzheimer's disease (AD) the increase of amyloid beta (Abeta42) in cerebrospinal fluid or plasma might be an initial event. We previously reported about the associations between concomitant medication and plasma Abeta42 levels in the non-demented population cohort of the Vienna transdanube aging study at baseline. In the present study, the longitudinal influence of insulin, gingko biloba, non-steroidal anti-inflammatory drugs (NSAIDs), oral anti-diabetics (sulfonylurea and biguanides), estrogens, fibrates, and statins on plasma Abeta42 are presented. Associated with medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42. Long-term users of gingko biloba, independent of their MTA, had significantly decreased plasma Abeta42 and the age-dependent increase of plasma Abeta42 was significantly smaller in long-term gingko biloba treated subjects. The use of fibrates also decreased plasma Abeta42 levels. In multiple testing considering interactions between medications, gender, APOE-epsilon4 presence and creatinine, insulin long-term users again showed significantly increased levels; fibrate and gingko biloba users showed a trend to rather decreased plasma Abeta42 levels compared to the non-users (p=0.05-0.08). Neither statins nor NSAIDs showed a significant effect on plasma Abeta42 in this model. Measuring the effect on cognition, no single medication studied was a significant predictor of conversion to AD or mild cognitive impairment (MCI). Whether the use of gingko biloba might prevent the conversion to MCI or AD needs to be proven in prospective, clinical trials.

Attems J, Preusser M, Grosinger-Quass M, Wagner L, Lintner F, Jellinger K. · Institute of Pathology, Otto Wagner Hospital, Baumgartner Hoehe, Vienna, Austria. · Neuropathol Appl Neurobiol. · Pubmed #17961140 No free full text.

Abstract: The pathological findings in Alzheimer's disease (AD) are partly attributed to alterations in calcium-binding protein (CBP) functions. We showed previously that immunoreactivity of secretagogin, a recently cloned CBP, in the human hippocampus is restricted to pyramidal neurones and that the amount of immunoreactive neurones does not differ between AD cases and controls. In this study we investigate the influence of hippocampal tau pathology on secretagogin expression in more details. The study group consisted of 26 cases with different degrees of neuropathologically confirmed AD pathology. Sections were incubated separately with secretagogin- and tau-specific antibodies, respectively. The amount of immunoreactive neurones and integral optical densities were assessed. In addition, double immunofluorescence for both secretagogin and tau was performed. No difference with respect to secretagogin immunoreactivity was observed in different stages of AD pathology, and similarly no significant associations were seen between the amount of secretagogin and tau immunoreactivity in the different hippocampal subfields. Double immunofluorescence revealed that both proteins rarely colocalize because only 5.3% of tau and 2.9% of secretagogin immunoreactive neurones, respectively, showed colocalization. Because there are no differences in the amount of hippocampal secretagogin expression between AD cases and controls (as we have shown previously), the lack of an association between the amount of secretagogin expression and tau burden together with the low frequency of colocalization of tau and secretagogin in the human hippocampus, suggest that secretagogin-expressing neurones are largely resistant to neurodegeneration in AD.

Dal Bianco A, Bradl M, Frischer J, Kutzelnigg A, Jellinger K, Lassmann H. · Center for Brain Research, Medical University of Vienna, Austria. · Ann Neurol. · Pubmed #17924575 No free full text.

Abstract: OBJECTIVE: Chronic inflammation with microglia activation is thought to play a major role in the formation or clearance of Alzheimer's disease (AD) lesions, as well as in the induction of demyelination in multiple sclerosis (MS). In MS, the cortex is severely affected by chronic, long-lasting inflammation, microglia activation, and demyelination. To what extent chronic inflammation in the cortex of MS patients influences the development of AD lesions is so far unresolved. METHODS: The study was performed on autopsy tissue of 45 MS cases, 9 AD cases, and 15 control subjects. We analyzed lymphocyte and plasma cell infiltration in relation to microglia activation, to the presence of beta-amyloid plaques and (AT8+) neurofibrillary tangles, and to myelin pathology. RESULTS: Profound microglia activation, determined by a broad spectrum of markers, was found in both MS and AD cortices, and the patterns of microglia activation were closely similar. Microglia activation in MS cortex, in contrast with that in AD and control cortex, correlated with lymphocyte and plasma-cell infiltrates in the meninges. MS cases older than 64 years experienced development of AD pathology in comparable incidence as seen in the course of normal aging. The density of beta-amyloid plaques and neurofibrillary tangles did not differ between demyelinated and nondemyelinated cortical areas. CONCLUSIONS: Our data suggest that microglia activation in the MS cortex alone has little or no influence on the development of cortical AD pathology.

Sofic E, Sapcanin A, Tahirovic I, Gavrankapetanovic I, Jellinger K, Reynolds GP, Tatschner T, Riederer P. · Department of Chemistry, Faculty of Science, University of Sarajevo, Bosnia & Herzegovina. · J Neural Transm Suppl. · Pubmed #17447414 No free full text.

Abstract: Oxidative stress has been associated with damage and progressive cell death that occurs in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). The aim of this study was to investigate the antioxidant capacity in postmortem motor cortex (MC), nucleus caudatus (NC), gyrus temporalis (GT) and substantia nigra (SN) from controls (C) and patients with PD and AD. The initial samples consisted of 68 subjects of PD, AD and C. Brains were matched for age, sex and postmortem time. Brain tissue was homogenized in a phosphate buffer pH 7.3 and separated with two-step centrifugation at 15,000rpm for 30 min and 15,000 rpm for 10 min at 4 degrees C. Antioxidant capacity in the supernatants was measured using the oxygen radical absorbance assay (ORAC). The results showed that in the SN of parkinsonian's brain the balance between production of free radicals and the neutralization by a complex antioxidant system is disturbed. No changes in the antioxidant capacity of postmortem MC and NC of parkinsonian's brain in comparison with C were found. In the SN of parkinsonian's brain, antioxidant capacity seems to be lower in comparison with C (p < 0.05). Antioxidant capacity against peroxyl radical showed that MC of AD patients was lower than in the MC of C (p < 0.005). In NC of AD patients the antioxidant capacity against hydroxyl radical was increased in comparison with C (p < 0.04). No changes in the antioxidant capacity were found in brain tissues of AD in comparison with C, when CuSO4 was used as a free radical generator.

Attems J, Quass M, Gartner W, Nabokikh A, Wagner L, Steurer S, Arbes S, Lintner F, Jellinger K. · Institute of Pathology, Otto Wagner Hospital, Baumgartner Hoehe 1A-1145, Vienna, Austria. · Exp Gerontol. · Pubmed #17116382 No free full text.

Abstract: Disturbed calcium homeostasis plays a crucial role in the aetiology of Alzheimer's disease (AD) and the aging process. We evaluated immunoreactivity of secretagogin, a recently cloned calcium binding protein, in hippocampus and adjacent entorhinal cortex of 30 neuropathologically examined post mortem brains (m:f=12:18; mean age, 79.8+/-15.1 years). The study group consisted of 15 cases fulfilling the criteria for high probability of AD according to the NIA-Reagan Institute Criteria and 15 cases with no to medium probability. Sections were incubated with secretagogin-specific antibodies and the number of immunoreactive neurons as well as staining intensities in both neurons and neuropil were assessed. Both cellular and neuropil immunoreactivity were restricted to subiculum and Ammons horn. Cellular immunoreactivity was further restricted to pyramidal neurons and showed a hierarchical distribution: the mean percentage of immunoreactive neurons was highest in sector CA3 (64.41%), followed by CA2 (44.09%), CA4 (34.38%), CA1 (10.9%), and the subiculum (2.92%; P<0.001, except CA2-CA4, P>0.05), while it did not differ significantly between groups with different degrees of AD pathology. The pattern of secretagogin immunoreactivity resembles that of calcium sensor proteins as it is restricted to a subset of neurons and therefore secretagogin could serve highly specialized tasks in neuronal calcium signalling.

Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I, Tragl KH, Fischer P. · Department of Psychiatry, Innsbruck Medical University, Austria. · Neurobiol Aging. · Pubmed #17055615 No free full text.

Abstract: The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Völkel W, Sicilia T, Pähler A, Gsell W, Tatschner T, Jellinger K, Leblhuber F, Riederer P, Lutz WK, Götz ME. · Department of Toxicology, University of Würzburg, Würzburg, Germany. · Neurochem Int. · Pubmed #16483694 No free full text.

Abstract: In the last decade an important role for the progression of neuronal cell death in Alzheimer's disease (AD) has been ascribed to oxidative stress. trans-4-Hydroxy-2-nonenal, a product of lipid peroxidation, forms conjugates with a variety of nucleophilic groups such as thiols or amino moieties. Here we report for the first time the quantitation of glutathione conjugates of trans-4-hydroxy-2-nonenal (HNEGSH) in the human postmortem brain using the specific and very sensitive method of electrospray ionization triple quadrupole mass spectrometry (ESI-MS-MS). Levels of HNEGSH conjugates calculated as the sum of three chromatographically separated diastereomers were determined in hippocampus, entorhinal cortex, substantia innominata, frontal and temporal cortex, as well as cerebellum from patients with AD and controls matched for age, gender, postmortem delay and storage time. Neither age, nor postmortem delay, nor storage time did correlate with levels of HNEGSH conjugates which ranged between 1 and 500 pmol/g fresh weight in the brain areas examined. The brain specimen from patients with clinically and neuropathologically probable AD diagnosed according to criteria of the consortium to establish a registry for AD (CERAD) show increased levels of HNEGSH in the temporal and frontal cortex, as well as in the substantia innominata. Classification of disease severity according to Braak and Braak, which takes into consideration the amount of neurofibrillary tangles and neuritic plaques, revealed highest levels of HNEGSH in the substantia innominata and the hippocampus, two brain regions known to be preferentially affected in AD. These results substantiate the link between conjugates of glutathione with a product of lipid peroxidation and Alzheimer's disease and justify further studies to evaluate the role of HNE metabolites as potential biomarkers for disease progression in AD.

Glatz DC, Rujescu D, Tang Y, Berendt FJ, Hartmann AM, Faltraco F, Rosenberg C, Hulette C, Jellinger K, Hampel H, Riederer P, Möller HJ, Andreadis A, Henkel K, Stamm S. · Molecular and Clinical Neurobiology, Department of Psychiatry Ludwig-Maximilians-University, Munich, Germany. · J Neurochem. · Pubmed #16371011 No free full text.

Abstract: Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in tauopathies, which include Alzheimer's disease (AD). Tau is a microtubule-associated protein whose transcript undergoes alternative splicing in the brain. Exon 10 encodes one of four microtubule-binding repeats. Exon 10 inclusion gives rise to tau protein isoforms containing four microtubule-binding repeats (4R) whereas exclusion leads to isoforms containing only three repeats (3R). The ratio between 3R and 4R isoforms is tightly controlled via alternative splicing in the human adult nervous system and distortion of this balance results in neurodegeneration. Previous studies showed that several splicing regulators, among them hTRA2-beta1 and CLK2, regulate exon 10 alternative splicing. Like most splicing factors, htra2-beta and clk2 pre-mRNAs are regulated by alternative splicing. Here, we investigated whether human postmortem brain tissue of AD patients reveal differences in alternative splicing patterns of the tau, htra2-beta, presenilin 2 and clk2 genes when compared with age-matched controls. We found that the splicing patterns of all four genes are altered in affected brain areas of sporadic AD patients. In these affected areas, the amount of mRNAs of tau isoforms including exon 10, the htra2-beta1 isoform and an inactive form of clk2 are significantly increased. These findings suggest that a misregulation of alternative splicing seems to contribute to sporadic AD.

Frölich L, Götz ME, Weinmüller M, Youdim MB, Barth N, Dirr A, Gsell W, Jellinger K, Beckmann H, Riederer P. · Division of Geriatric Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Germany. · J Neural Transm. · Pubmed #14991456 No free full text.

Abstract: In dementia of Alzheimer type (DAT), cerebral glucose metabolism is reduced in vivo, and enzymes involved in glucose breakdown are impaired in post-mortem brain tissue. Pyruvate dehydrogenase complex activity (PDHc) is one of the enzymes known to be reduced, while succinate dehydrogenase activity (SDH), another enzyme of oxidative glucose metabolism is unchanged. In dementia of vascular type (DVT), variable changes in glucose metabolism have been demonstrated in vivo, while changes of enzyme activities in post-mortem brain tissue are unknown. Here, PDHc and SDH activity were stimulated with each of the two stereoisomers of alpha lipoic acid in post-mortem parietal brain cortex of patients with DAT, DVT, and one case of Pick's disease and compared to stimulation effects in a control group, matched for age, sex, post-mortem delay, and storage time of brain tissue. PDHc in DAT and DVT, but not in Pick's disease was reduced. PDHc activity could be slightly stimulated by 10 micro M of the physiological stereoisomer (r)-alpha-lipoic acid, in controls and DVT (possibly also in Pick's disease), but not in DAT. In all groups investigated SDH was activated by 100 micro M and 1 mM of both isomers of alpha-lipoic acid, whereas 10 mM of both stereoisomers of alpha-lipoic acid caused an inhibition of both, PDHc and SDH activity. The loss of basal and of (r)-alpha-lipoic acid stimulated PDHc activity indicate that a functional or structural impairment of PDHc may exist in DAT and DVT which is not merely attributable to loss of mitochondria since basal and stimulated SDH activities are similar in controls, DVT and DAT, thus indicating selective vulnerability of PDHc.

Kienzl E, Jellinger K, Janetzky B, Steindl H, Bergmann J. · Vienna Health Board and L. B. Institute of Clinical Neurobiology, Vienna, Austria. · J Neural Transm Suppl. · Pubmed #12456054 No free full text.

Abstract: Recently, a novel risk gene protein expressed in elderly patients with the diagnosis of Alzheimer disease (AD) was discovered on chromosome 21 within the APP (amyloid precursor protein) region. This 79 amino acid protein, ALZAS (Alzheimer Associated Protein) contains the beta-amyloid peptide 1-42 fragment, the APP transmembrane signal, and a unique 12 amino acid c-terminal which is not present in any known allele of the APP gene. Reverse transcription-PCR revealed that the transcript of ALZAS was expressed in cortical and hippocampal regions of human Alzheimer disease brain as well as in leukocytes derived from AD patients. Most specifically, an endogenous antibody was found in patients with confirmed AD, in patients with depression, and in subjects suggested to have presymptomatic AD, where it was directed against epitopes within the intron encoded amino acid c-terminal sequence.

Götz ME, Wacker M, Luckhaus C, Wanek P, Tatschner T, Jellinger K, Leblhuber F, Ransmayr G, Riederer P, Eder E. · Department of Toxicology, University of Würzburg, Germany. · Neurosci Lett. · Pubmed #11983292 No free full text.

Abstract: In recent years, an important role for the pathogenesis of Alzheimer's disease (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product of lipid peroxidation, forms stable adducts with a variety of nucleophilic substituents such as thiols or amino moieties. Here, we report the quantification of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp) using the specific and very sensitive method of 32P-postlabeling of deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the hippocampus, the parietal cortex, and the cerebellum of postmortem brains from patients with AD and age matched controls. Adduct levels were highest in the hippocampus, followed by the cerebellum and parietal cortex irrespective of the disease. Neither age, postmortem delay time, gender, nor the extent of neurofibrillary deposits affected tissue adduct levels in the brain areas examined. Although distinctively present in the human brain, the level of HNE-dGp adducts appears not to be useful as a biomarker for AD.

Stadelmann C, Deckwerth TL, Srinivasan A, Bancher C, Brück W, Jellinger K, Lassmann H. · Department of Neuroimmunology, University of Vienna, Vienna, Austria. · Am J Pathol. · Pubmed #10550301 links to  free full text

Abstract: Neuronal loss is prominent in Alzheimer's disease (AD), and its mechanisms remain unresolved. Apoptotic cell death has been implicated on the basis of studies demonstrating DNA fragmentation and an up-regulation of proapoptotic proteins in the AD brain. However, DNA fragmentation in neurons is too frequent to account for the continuous neuronal loss in a degenerative disease extending over many years. Furthermore, the typical apoptotic morphology has not been convincingly documented in AD neurons with fragmented DNA. We report the detection of the activated form of caspase-3, the central effector enzyme of the apoptotic cascade, in AD and Down's syndrome (DS) brain using an affinity-purified antiserum. In AD and DS, single neurons with apoptotic morphology showed cytoplasmic immunoreactivity for activated caspase-3, whereas no neurons were labeled in age-matched controls. Apoptotic neurons were identified at an approximate frequency of 1 in 1100 to 5000 neurons in the cases examined. Furthermore, caspase-3 immunoreactivity was detected in granules of granulovacuolar degeneration. Our results provide direct evidence for apoptotic neuronal death in AD with a frequency compatible with the progression of neuronal degeneration in this chronic disease and identify autophagic vacuoles of granulovacuolar degeneration as possible means for the protective segregation of early apoptotic alterations in the neuronal cytoplasm.

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.

Jellinger K. · No affiliation provided · Neurology. · Pubmed #11865164 No free full text.

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Jellinger K. · No affiliation provided · Neuropathol Appl Neurobiol. · Pubmed #11123724 No free full text.

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Jellinger K. · No affiliation provided · Neurology. · Pubmed #10980757 No free full text.

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Jellinger K. · No affiliation provided · J Neurol Neurosurg Psychiatry. · Pubmed #10877632 links to  free full text

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