Consensus Paper of the WFSBP Task Force on Biological Markers of Dementia: The role of CSF and blood analysis in the early and differential diagnosis of dementia

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Aβ peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

[1]  Harald Hampel,et al.  CSF total tau, Aβ42 and phosphorylated tau protein as biomarkers for Alzheimer’s disease , 2001, Molecular Neurobiology.

[2]  Juan Manuel Maler,et al.  Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease , 2007, Journal of Molecular Neuroscience.

[3]  F. Gemignani,et al.  Platelet monoamine oxidase molecular activity in demented patients , 1997, The Italian Journal of Neurological Sciences.

[4]  S. Poser,et al.  Chronic HIV encephalitis — II. clinical aspects , 1988, Klinische Wochenschrift.

[5]  S. Poser,et al.  Chronic HIV encephalitis — I. cerebrospinal fluid diagnosis , 1988, Klinische Wochenschrift.

[6]  A. Sartorius,et al.  Mechanisms of depression: the role of neurogenesis , 2004 .

[7]  K. Blennow,et al.  Increased cerebrospinal fluid levels of transforming growth factor-β1 in Alzheimer’s disease , 2004, Neuroscience Letters.

[8]  P. Scheltens,et al.  Amyloid β(1–42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease , 2004, Neurology.

[9]  David P. Kreil,et al.  Determining a significant change in protein expression with DeCyder™ during a pair‐wise comparison using two‐dimensional difference gel electrophoresis , 2004, Proteomics.

[10]  I. Grundke‐Iqbal,et al.  Role of tau phosphorylation by glycogen synthase kinase-3β in the regulation of organelle transport , 2004, Journal of Cell Science.

[11]  P. Lewczuk,et al.  Amyloid β peptides in cerebrospinal fluid as profiled with surface enhanced laser desorption/ionization time-of-flight mass spectrometry: evidence of novel biomarkers in Alzheimer's disease , 2004, Biological Psychiatry.

[12]  Juan Manuel Maler,et al.  Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau , 2004, Neurobiology of Aging.

[13]  P. Lewczuk,et al.  Electrophoretic separation of amyloid beta peptides in plasma. , 2004, Electrophoresis.

[14]  P. Scheltens,et al.  Amyloid beta(1-42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease. , 2004, Neurology.

[15]  H. Takeuchi Whipple disease , 2020, Definitions.

[16]  H. Kimura,et al.  Expression of monoamine oxidase B activity in astrocytes of senile plaques , 2004, Acta Neuropathologica.

[17]  B. Winblad,et al.  Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis , 2004, Acta Neuropathologica.

[18]  Katharina Buerger,et al.  Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. , 2004, Archives of general psychiatry.

[19]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[20]  Henrik Zetterberg,et al.  Cerebrospinal fluid markers for prediction of Alzheimer's disease , 2003, Neuroscience Letters.

[21]  E. Eşel,et al.  A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome , 2003, Psychiatry Research: Neuroimaging.

[22]  J. Trojanowski,et al.  Biological markers for therapeutic trials in Alzheimer’s disease Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer’s disease , 2003, Neurobiology of Aging.

[23]  P. Lewczuk,et al.  The amyloid-β (Aβ) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Aβ peptide , 2003 .

[24]  Trey Sunderland,et al.  Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. , 2003, JAMA.

[25]  Kaj Blennow,et al.  Cerebrospinal fluid levels of total‐tau, phospho‐tau and Aβ42 predicts development of Alzheimer's disease in patients with mild cognitive impairment , 2003 .

[26]  H. Möller,et al.  Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. , 2003, The American journal of psychiatry.

[27]  Kaj Blennow,et al.  Cerebrospinal fluid levels of total-tau, phospho-tau and A beta 42 predicts development of Alzheimer's disease in patients with mild cognitive impairment. , 2003, Acta neurologica Scandinavica. Supplementum.

[28]  H. Braak,et al.  Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism. , 2003, Archives of neurology.

[29]  A. Bechara,et al.  Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward? , 2002, Neuropsychologia.

[30]  K. Blennow,et al.  Cerebrospinal Fluid Phospho-Tau, Total Tau and β-Amyloid1–42 in the Differentiation between Alzheimer’s Disease and Vascular Dementia , 2002, Dementia and Geriatric Cognitive Disorders.

[31]  N. Shahani,et al.  Functions and malfunctions of the tau proteins , 2002, Cellular and Molecular Life Sciences CMLS.

[32]  M. Buchsbaum Regional cerebral blood flow changes in drug-resistant depressed patients following treatment with transcranial magnetic stimulation: a statistical parametric mapping analysis. , 2002, Psychiatry research.

[33]  I. Grundke‐Iqbal,et al.  Significance and mechanism of alzheimer neurofibrillary degeneration and therapeutic targets to inhibit this lesion , 2002, Journal of Molecular Neuroscience.

[34]  Katharina Buerger,et al.  Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. , 2002, Archives of neurology.

[35]  J. Trojanowski,et al.  Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. , 2002, Archives of neurology.

[36]  J. Kornhuber,et al.  Highly conserved and disease‐specific patterns of carboxyterminally truncated Aβ peptides 1–37/38/39 in addition to 1–40/42 in Alzheimer's disease and in patients with chronic neuroinflammation , 2002, Journal of neurochemistry.

[37]  K. Blennow,et al.  CSF‐Phospho‐tau (181P) as a Promising Marker for Discriminating Alzheimer's Disease from Dementia with Lewy Bodies , 2002 .

[38]  I. Grundke‐Iqbal,et al.  Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients : an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay. , 2002, The American journal of pathology.

[39]  E. Mandelkow,et al.  Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress , 2002, The Journal of cell biology.

[40]  Anders Wallin,et al.  Increased intrathecal levels of the angiogenic factors VEGF and TGF-β in Alzheimer’s disease and vascular dementia , 2002, Neurobiology of Aging.

[41]  Sudha Seshadri,et al.  Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease , 2002 .

[42]  R. Bullock New drugs for Alzheimer's disease and other dementias , 2002, British Journal of Psychiatry.

[43]  D. Dickstein,et al.  p97 as a biomarker for Alzheimer disease. , 2002, Frontiers in bioscience : a journal and virtual library.

[44]  P. Fischer,et al.  Vienna Transdanube Aging "VITA": study design, recruitment strategies and level of participation. , 2002, Journal of neural transmission. Supplementum.

[45]  E. Rüther,et al.  Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells* , 2001, The Journal of Biological Chemistry.

[46]  K. Blennow,et al.  Low cerebrospinal fluid β-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment , 2001, Neuroscience Letters.

[47]  Patrick L. McGeer,et al.  Inflammation, autotoxicity and Alzheimer disease , 2001, Neurobiology of Aging.

[48]  Daniel J Buysse,et al.  Tolerability of Combined Treatment With Lithium and Paroxetine in Patients With Bipolar Disorder and Depression , 2001, Journal of clinical psychopharmacology.

[49]  K. Blennow,et al.  Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values. , 2001, Clinical chemistry.

[50]  E. Hollander,et al.  New developments in impulsivity , 2001, The Lancet.

[51]  D. Knopman,et al.  Pharmacotheraphy for Alzheimer’s disease , 2001, Current neurology and neuroscience reports.

[52]  C. Conway,et al.  The combined use of bupropion, lithium, and venlafaxine during ECT: a case of prolonged seizure activity. , 2001, The journal of ECT.

[53]  Alan C. Evans,et al.  Changes in brain activity related to eating chocolate: from pleasure to aversion. , 2001, Brain : a journal of neurology.

[54]  L. Oreland,et al.  Genetic mechanisms of behavior—don't forget about the transcription factors , 2001, Molecular Psychiatry.

[55]  H. Reiber,et al.  Dynamics of brain-derived proteins in cerebrospinal fluid. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[56]  Katharina Buerger,et al.  Large‐scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease , 2001, Annals of neurology.

[57]  L. Szirovicza,et al.  Similarities in the pattern of regional brain dysfunction in negative schizophrenia and unipolar depression: a single photon emission-computed tomography and auditory evoked potentials study , 2001, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[58]  William Marslen-Wilson,et al.  Does the Medial Temporal Lobe Bind Phonological Memories? , 2001, Journal of Cognitive Neuroscience.

[59]  Virginia M. Y. Lee,et al.  Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis , 2001, The Journal of Neuroscience.

[60]  Jeffrey L. Cummings,et al.  Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2001 .

[61]  B. Miller,et al.  CME Practice parameter : Diagnosis of dementia ( an evidence-based review ) Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2001 .

[62]  S. Rapoport,et al.  Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231 , 2001, Annals of neurology.

[63]  J. Kornhuber,et al.  Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies , 2001, Gerontology.

[64]  M. Vitek,et al.  Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. , 2001, Journal of cell science.

[65]  M. Thase,et al.  Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. , 2001, JAMA.

[66]  K. Blennow,et al.  Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. , 2001, Archives of neurology.

[67]  Hansotto Reiber,et al.  Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs , 2001, Journal of the Neurological Sciences.

[68]  L. Parnetti,et al.  CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies , 2001, Neurological Sciences.

[69]  K. Blennow,et al.  Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke , 2001, Neuroscience Letters.

[70]  Wei Zheng Neurotoxicology of the Brain Barrier System: New Implications , 2001, Journal of toxicology. Clinical toxicology.

[71]  L. Krahn,et al.  Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia. , 2001, The Journal of clinical psychiatry.

[72]  E. Rolls,et al.  Abstract reward and punishment representations in the human orbitofrontal cortex , 2001, Nature Neuroscience.

[73]  U. Pettersson,et al.  Investigation of the functional effect of monoamine oxidase polymorphisms in human brain , 2001, Human Genetics.

[74]  M. Egan,et al.  Memory for temporal order in patients with schizophrenia , 2000, Schizophrenia Research.

[75]  L. Nystrom,et al.  Tracking the hemodynamic responses to reward and punishment in the striatum. , 2000, Journal of neurophysiology.

[76]  Nobuyuki Okamura,et al.  CSF Phosphorylated Tau Protein and Mild Cognitive Impairment: A Prospective Study , 2000, Experimental Neurology.

[77]  A. Mortimer,et al.  Somatic treatment of psychotic depression: review and recommendations for practice. , 2000, Journal of clinical psychopharmacology.

[78]  D. Vignali Multiplexed particle-based flow cytometric assays. , 2000, Journal of immunological methods.

[79]  Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes , 2000, The Journal of cell biology.

[80]  J. Stewart Lithium and maintenance ECT. , 2000, The journal of ECT.

[81]  J. J. Visser,et al.  Genetic and biochemical markers for Alzheimer's disease: recent developments , 2000, Annals of clinical biochemistry.

[82]  Karl J. Friston,et al.  Dissociable Neural Responses in Human Reward Systems , 2000, The Journal of Neuroscience.

[83]  Patrick R. Hof,et al.  Tau protein isoforms, phosphorylation and role in neurodegenerative disorders 1 1 These authors contributed equally to this work. , 2000, Brain Research Reviews.

[84]  S. Clark,et al.  Pediatrician and family physician prescription of selective serotonin reuptake inhibitors. , 2000, Pediatrics.

[85]  Igor Nenadic,et al.  Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task , 2000, Schizophrenia Research.

[86]  K. Blennow,et al.  Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization , 2000, Neuroscience Letters.

[87]  M Rovaris,et al.  MRI correlates of cognitive dysfunction in multiple sclerosis patients. , 2000, Journal of neurovirology.

[88]  H. Vanderstichele,et al.  Cerebrospinal beta-amyloid (1–42) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline , 2000, Neuroscience Letters.

[89]  S. Weinberger,et al.  Recent advancements in surface‐enhanced laser desorption/ionization‐time of flight‐mass spectrometry , 2000, Electrophoresis.

[90]  J. Kornhuber,et al.  Decreased β-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease , 2000, Neurology.

[91]  R. Veerhuis,et al.  Neuroinflammation and Alzheimer disease: clinical and therapeutic implications. , 2000, Alzheimer disease and associated disorders.

[92]  L. Zhou,et al.  Amyloid-beta 25-35 peptide induces expression of monoamine oxidase B in cultured rat astrocytes. , 2000, Acta pharmacologica Sinica.

[93]  R. Samanin,et al.  Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain , 1999, British journal of pharmacology.

[94]  K. Blennow,et al.  Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. , 1999, Neurology.

[95]  T. Robbins,et al.  Choosing between Small, Likely Rewards and Large, Unlikely Rewards Activates Inferior and Orbital Prefrontal Cortex , 1999, The Journal of Neuroscience.

[96]  J. Lee,et al.  Positive and negative symptoms and regional cerebral perfusion in antipsychotic-naive schizophrenic patients: a high-resolution SPECT study , 1999, Psychiatry Research: Neuroimaging.

[97]  D J Stephens,et al.  The role of cholesterol in the biosynthesis of beta-amyloid. , 1999, Neuroreport.

[98]  P. Gaszner,et al.  Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. , 1999, The Journal of clinical psychiatry.

[99]  P. Deyn,et al.  Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF , 1999, Neurology.

[100]  B. Thies,et al.  Consensus report of the Working Group on: molecular and biochemical markers of Alzheimer's disease. , 1999 .

[101]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[102]  K. Willmes,et al.  Active and remitted schizophrenia: psychopathological and regional cerebral blood flow findings , 1999, Psychiatry Research: Neuroimaging.

[103]  C. de Montigny,et al.  Modulation of noradrenergic neuronal firing by selective serotonin reuptake blockers , 1999, British journal of pharmacology.

[104]  J. Kelly,et al.  Activity and onset of action of reboxetine and effect of combination with sertraline in an animal model of depression. , 1999, European journal of pharmacology.

[105]  E. Rüther,et al.  Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life. , 1999, Journal of child and adolescent psychopharmacology.

[106]  J. Gruzelier,et al.  Functional neuropsychophysiological asymmetry in schizophrenia: a review and reorientation. , 1999, Schizophrenia bulletin.

[107]  R. Gur,et al.  Laterality in functional brain imaging studies of schizophrenia. , 1999, Schizophrenia bulletin.

[108]  J. Shih,et al.  Transcription factor binding to the core promoter of the human monoamine oxidase B gene in the cerebral cortex and in blood cells , 1998, Neuroscience Letters.

[109]  Cheuk Y. Tang,et al.  A method of basal forebrain anatomical standardization for functional image analysis , 1998, Psychiatry Research: Neuroimaging.

[110]  S. Gupta,et al.  Lithium and Maintenance Electroconvulsive Therapy , 1998, The journal of ECT.

[111]  Khadija Iqbal,et al.  Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. , 1998, Archives of biochemistry and biophysics.

[112]  Y. Mateo,et al.  Somatodendritic α2‐Adrenoceptors in the Locus Coeruleus Are Involved in the In Vivo Modulation of Cortical Noradrenaline Release by the Antidepressant Desipramine , 1998, Journal of neurochemistry.

[113]  J. Mikkelsen,et al.  Long-term effects on serotonin transporter mRNA expression of chronic neonatal exposure to a serotonin reuptake inhibitor. , 1998, European journal of pharmacology.

[114]  J. Kaye,et al.  High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. , 1998, Archives of neurology.

[115]  S. Hirai,et al.  Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan , 1998 .

[116]  D. Riesner,et al.  Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer's patients by fluorescence correlation spectroscopy , 1998, Nature Medicine.

[117]  H. Reiber,et al.  The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis , 1998, Multiple sclerosis.

[118]  D. Brooks,et al.  Evidence for striatal dopamine release during a video game , 1998, Nature.

[119]  Giovanni B. Frisoni,et al.  Consensus report of the working group on: 'Molecular and biochemical markers of Alzheimer's disease' , 1998 .

[120]  R. Mayeux Evaluation and Use of Diagnostic Tests in Alzheimer’s Disease , 1998, Neurobiology of Aging.

[121]  P. Riederer,et al.  Platelet Monoamine Oxidase B Activity in Dementia , 1998, Dementia and Geriatric Cognitive Disorders.

[122]  A D Roses,et al.  Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease. , 1998, The New England journal of medicine.

[123]  H. Damasio,et al.  Dissociation Of Working Memory from Decision Making within the Human Prefrontal Cortex , 1998, The Journal of Neuroscience.

[124]  Nancy Reagan,et al.  Consensus Report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease" , 1998 .

[125]  P. Riederer,et al.  Platelet monoamine oxidase B activity in dementia. A 4-year follow-up. , 1998, Dementia and geriatric cognitive disorders.

[126]  S. Hirai,et al.  Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan. , 1998, Annals of neurology.

[127]  P. Panegyres The amyloid precursor protein gene: a neuropeptide gene with diverse functions in the central nervous system , 1997, Neuropeptides.

[128]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[129]  N. Andreasen,et al.  Effect of Antipsychotics on Regional Cerebral Blood Flow Measured with Positron Emission Tomography , 1997, Neuropsychopharmacology.

[130]  K. Rhodes,et al.  Selective Aggregation of Endogenous β‐Amyloid Peptide and Soluble Amyloid Precursor Protein in Cerebrospinal Fluid by Zinc , 1997, Journal of neurochemistry.

[131]  E. Klein,et al.  Effect of single and repeated administration of fluvoxamine on noradrenaline release in rat brain. , 1997, European journal of pharmacology.

[132]  J. Kornhuber,et al.  Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease , 1997, Neuroscience Letters.

[133]  C. Hock,et al.  Dependence of cerebrospinal fluid Tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer's disease , 1997, Neuroscience Letters.

[134]  C. Montigny,et al.  The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments , 1997, Brain Research Reviews.

[135]  C Dickmann,et al.  Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[136]  C. de Montigny,et al.  Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5‐hydroxtryptamine system , 1997, British journal of pharmacology.

[137]  P. Lansbury,et al.  Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. , 1997, Annual review of biochemistry.

[138]  H. Feldman,et al.  Serum levels of the iron binding protein p97 are elevated in Alzheimer′s disease , 1996, Nature Medicine.

[139]  S. Fahn,et al.  Diagnostic guidelines in central nervous system Whipple's disease , 1996, Annals of neurology.

[140]  L. Wahlund,et al.  Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele ϵ4 during 14 months follow-up , 1996, Neuroscience Letters.

[141]  Khadija Iqbal,et al.  Calcium/calmodulin‐dependent protein kinase II phosphorylates tau at Ser‐262 but only partially inhibits its binding to microtubules , 1996, FEBS letters.

[142]  Monte S. Buchsbaum,et al.  Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia , 1996, Schizophrenia Research.

[143]  M S Buchsbaum,et al.  PET and MRI of the thalamus in never-medicated patients with schizophrenia. , 1996, The American journal of psychiatry.

[144]  P. Fenwick,et al.  Negative Interaction between Lithium and Electroconvulsive Therapy – A Case-Control Study , 1996, British Journal of Psychiatry.

[145]  R. Wolfert,et al.  Reduction of β‐amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease , 1995 .

[146]  M. Rebhan,et al.  Developmental expression of tau proteins in the chicken and rat brain: Rapid down-regulation of a paired helical filament epitope in the rat cerebral cortex coincides with the transition from immature to adult tau isoforms , 1995, International Journal of Developmental Neuroscience.

[147]  J. Trojanowski,et al.  Tau in cerebrospinal fluid: A potential diagnostic marker in Alzheimer's disease , 1995, Annals of neurology.

[148]  H. Reiber,et al.  Relevance of cerebrospinal fluid variables for early diagnosis of neuroborreliosis , 1995, Neurology.

[149]  H. Folkerts Spontaneous seizure after concurrent use of methohexital anesthesia for electroconvulsive therapy and paroxetine: a case report. , 1995, The Journal of nervous and mental disease.

[150]  J. Lauder Ontogeny of neurotransmitter systems: Substrates for developmental disabilities? , 1995 .

[151]  D. Galasko,et al.  Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. , 1995, Annals of neurology.

[152]  J. Trojanowski,et al.  The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases. , 1994, The Journal of biological chemistry.

[153]  B. Fallon,et al.  Lyme disease: a neuropsychiatric illness. , 1994, The American journal of psychiatry.

[154]  Practice parameter for diagnosis and evaluation of dementia (Summary statement) , 1994, Neurology.

[155]  V. Chan‐Palay,et al.  Increased monoamine oxidase b activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography , 1994, Neuroscience.

[156]  M. Eigen,et al.  Sorting single molecules: application to diagnostics and evolutionary biotechnology. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[157]  N. Hirokawa,et al.  Altered microtubule organization in small-calibre axons of mice lacking tau protein , 1994, Nature.

[158]  L. Parnetti,et al.  Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders , 1994, Aging.

[159]  P. Fischer,et al.  Platelet monoamine oxidase B activity and vitamin B12 in dementia , 1994, Biological Psychiatry.

[160]  J. Hyttel Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs) , 1994, International clinical psychopharmacology.

[161]  D. Selkoe,et al.  Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. , 1994, Annual review of cell biology.

[162]  A. Wallin,et al.  Low frequency of post‐lumbar puncture headache in demented patients , 1993, Acta neurologica Scandinavica.

[163]  C. Masters,et al.  Regulation and Expression of the Alzheimer's β/A4 Amyloid Protein Precursor in Health, Disease, and Down's Syndrome a , 1993, Annals of the New York Academy of Sciences.

[164]  S. Damodaran Severity of family distress of schizophrenia—fact or artifact? , 1993, Acta psychiatrica Scandinavica.

[165]  M. Pericak-Vance,et al.  Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[166]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[167]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[168]  P. Riederer,et al.  The Therapeutic Place and Value of Present and Future MAO-B Inhibitors — l-Deprenyl as the Gold Standard , 1993 .

[169]  D. Murphy,et al.  Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants. , 1993, Brain research. Molecular brain research.

[170]  J. Wands,et al.  Neuronal thread protein over-expression in brains with Alzheimer's disease lesions , 1992, Journal of the Neurological Sciences.

[171]  S. Hauser,et al.  Increased levels of neuronal thread protein in cerebrospinal fluid of patients with Alzheimer's disease , 1992, Annals of neurology.

[172]  J. Brodie,et al.  Negative symptoms and hypofrontality in chronic schizophrenia. , 1992, Archives of general psychiatry.

[173]  G. Koob Dopamine, addiction and reward , 1992 .

[174]  Bradley T. Hyman,et al.  Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease , 1992, Neurology.

[175]  Karl J. Friston,et al.  Patterns of Cerebral Blood Flow in Schizophrenia , 1992, British Journal of Psychiatry.

[176]  T. Goldberg,et al.  Forms of memory failure in schizophrenia. , 1992 .

[177]  L. Oreland,et al.  Monoamine oxidase B in brains from patients with Alzheimer's disease: A biochemical and autoradiographical study , 1991, Neuroscience.

[178]  K. Kosik,et al.  Processes induced by tau expression in Sf9 cells have an axon-like microtubule organization , 1991, The Journal of cell biology.

[179]  K. Kosik,et al.  Overexpression of tau in a nonneuronal cell induces long cellular processes , 1991, The Journal of cell biology.

[180]  D. Wong,et al.  Affinities of fluoxetine, its enantiomers, and other inhibitors of serotonin uptake for subtypes of serotonin receptors. , 1991, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[181]  Markesbery Wr,et al.  Alterations in Brain Monoamine Oxidase Activity in Aging, Alzheimer's Disease, and Pick's Disease , 1991 .

[182]  H. Sternbach The serotonin syndrome. , 1991, The American journal of psychiatry.

[183]  B. Roth,et al.  Developmental regulation of 5-HT2 and 5-HT1c mRNA and receptor levels. , 1991, Brain research. Developmental brain research.

[184]  D. Sparks,et al.  Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease. , 1991, Archives of neurology.

[185]  V. Neuhoff,et al.  A new multiphasic buffer system for sodium dodecyl sulfate‐polyacrylamide gel electrophoresis of proteins and peptides with molecular masses 100 000–1000, and their detection with picomolar sensitivity , 1991, Electrophoresis.

[186]  J. Small,et al.  Lithium interactions: lithium and electroconvulsive therapy. , 1990, Journal of clinical psychopharmacology.

[187]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[188]  X. Breakefield,et al.  Biochemistry and genetics of monoamine oxidase. , 1990, Pharmacology & therapeutics.

[189]  S. Dinwiddie,et al.  Concurrent and Close Temporal Administration of Lithium and ECT. , 1990, Convulsive therapy.

[190]  P. Piccini,et al.  Increased platelet 3H-imipramine binding and monoamine oxidase B activity in Alzheimer's disease , 1990, Journal of neural transmission. Parkinson's disease and dementia section.

[191]  T. Crow Temporal lobe asymmetries as the key to the etiology of schizophrenia. , 1990, Schizophrenia bulletin.

[192]  M S Buchsbaum,et al.  The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. , 1990, Schizophrenia bulletin.

[193]  T. Goldberg,et al.  Recall memory deficit in schizophrenia A possible manifestation of prefrontal dysfunction , 1989, Schizophrenia Research.

[194]  L. DeLisi,et al.  Increased temporal lobe glucose use in chronic schizophrenic patients , 1989, Biological Psychiatry.

[195]  R. Gur,et al.  Laterality and frontality of cerebral blood flow and metabolism in schizophrenia: Relationship to symptom specificity , 1989, Psychiatry Research.

[196]  Riva,et al.  Effect of reboxetine, a new antidepressant drug, on the central noradrenergic system: Behavioural and biochemical studies , 1989 .

[197]  S. Poser,et al.  Chronic HIV encephalitis , 1988, Journal of Neuroimmunology.

[198]  P. Riederer,et al.  Platelet MAO‐B activity and the psychopathology of Parkinson's disease, senile dementia and multi‐infarct dementia , 1988, Acta psychiatrica Scandinavica.

[199]  T. Bolwig,et al.  Blood‐brain barrier studies with special reference to epileptic seizures , 1988, Acta psychiatrica Scandinavica. Supplementum.

[200]  G. Alexopoulos,et al.  Platelet MAO activity in geriatric patients with depression and dementia. , 1987, The American journal of psychiatry.

[201]  N. Volkow,et al.  Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia. , 1987, The American journal of psychiatry.

[202]  K. Grzeschik,et al.  The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor , 1987, Nature.

[203]  B. Navia,et al.  The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. , 1987, Archives of neurology.

[204]  L. Oreland,et al.  Brain and brain monoamine oxidase in aging and in dementia of Alzheimer's type , 1986, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[205]  Stephen M. Rao,et al.  Neuropsychology of multiple sclerosis: a critical review. , 1986, Journal of clinical and experimental neuropsychology.

[206]  B. Winblad,et al.  DEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE , 1986, The Lancet.

[207]  H. Wiśniewski,et al.  Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[208]  B. Winblad,et al.  Biochemical changes in Dementia disorders of Alzheimer type (AD/SDAT) , 1983, Neurobiology of Aging.

[209]  K. Bhargava,et al.  Increased permeability of blood brain barrier after electro-convulsive shocks (ECS). , 1982, Pharmacological research communications.

[210]  Robert C. Smith,et al.  Platelet Monoamine Oxidase in Alzheimer's Disease , 1982 .

[211]  N C Andreasen,et al.  Negative symptoms in schizophrenia , 1982 .

[212]  J. Gordon,et al.  Platelet monamine oxidase in Alzheimer's disease. , 1982, Journal of gerontology.

[213]  A. Coppen,et al.  Lithium Continuation Therapy Following Electroconvulsive Therapy , 1981, British Journal of Psychiatry.

[214]  B. Winblad,et al.  Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type. , 1980, Life sciences.

[215]  J. Small,et al.  Complications with electroconvulsive treatment combined with lithium. , 1980, Biological psychiatry.

[216]  D. Ingvar,et al.  Distribution of cerebral activity in chronic schizophrenia. , 1974, Lancet.

[217]  L. Stein Neurochemistry of reward and punishment: some implications for the etiology of schizophrenia. , 1971, Journal of psychiatric research.

[218]  C. Schnaitman,et al.  AN APPRAISAL OF THE USE OF MONOAMINE OXIDASE AS AN ENZYME MARKER FOR THE OUTER MEMBRANE OF RAT LIVER MITOCHONDRIA , 1970, The Journal of cell biology.

[219]  T. Tokizane [Physiological basis of consciousness]. , 1968, Geka chiryo. Surgical therapy.

[220]  H. Kuhlenbeck The human diencephalon; a summary of development, structure, function, and pathology. , 1954, Confinia neurologica.