β-Amyloid (Aβ) protein in cerebrospinal fluid as a biomarker for Alzheimer’s disease

Abstract With the arrival of symptomatic treatment (acetylcholine esterase inhibitors) and the promise of drugs that may delay disease progression, development of diagnostic biomarkers for Alzheimer’s disease (AD) are important. β-Amyloid (Aβ) protein is the main component of senile plaques. A marked reduction in cerebrospinal fluid (CSF)-Aβ42 in AD has been found in numerous studies. Importantly, reduced CSF-Aβ42 is also found very early in the disease process, before the onset of clinical symptoms. Recent studies suggest that CSF-Aβ42 have a satisfactory performance when used as a diagnostic marker for AD in clinical routine. This paper reviews CSF-Aβ42 as a biomarker for AD.

[1]  S. Hirai,et al.  Combination assay of CSF Tau, Aβ1-40 and Aβ1-42(43) as a biochemical marker of Alzheimer's disease , 1998, Journal of the Neurological Sciences.

[2]  P. Cras,et al.  Decreased Levels of Amyloid-beta 1-42 in Cerebrospinal Fluid of Creutzfeldt-Jakob Disease Patients. , 1999, Journal of Alzheimer's disease : JAD.

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

[4]  B. Ghetti,et al.  Low cerebrospinal-fluid concentrations of soluble amyloid β-protein precursor in hereditary Alzheimer's disease , 1992, The Lancet.

[5]  Hans Förstl,et al.  Analysis of Heterogeneous βA4 Peptides in Human Cerebrospinal Fluid and Blood by a Newly Developed Sensitive Western Blot Assay* , 1996, The Journal of Biological Chemistry.

[6]  Hilkka Soininen,et al.  Relationship between apoE genotype and CSF β-amyloid (1–42) and tau in patients with probable and definite Alzheimer’s disease , 2000, Neurobiology of Aging.

[7]  D. Selkoe,et al.  Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity , 1999, Nature.

[8]  B Engvall,et al.  Cerebrospinal fluid Aβ42 is increased early in sporadic Alzheimer's disease and declines with disease progression , 1999, Annals of neurology.

[9]  Joseph D. Buxbaum,et al.  Evidence That Tumor Necrosis Factor α Converting Enzyme Is Involved in Regulated α-Secretase Cleavage of the Alzheimer Amyloid Protein Precursor* , 1998, The Journal of Biological Chemistry.

[10]  Khadija Iqbal,et al.  Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. , 1993, Archives of biochemistry and biophysics.

[11]  G. Glenner,et al.  Differences Between Vascular and Plaque Core Amyloid in Alzheimer's Disease , 1988, Journal of neurochemistry.

[12]  H. Wiśniewski,et al.  Plasma and cerebrospinal fluid Levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease , 2000 .

[13]  D. Selkoe,et al.  Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids , 1992, Nature.

[14]  J. Treanor,et al.  Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. , 1999, Science.

[15]  G. Glenner,et al.  Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Galasko,et al.  Amyloid-beta peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma. , 2000, Biochemical and biophysical research communications.

[17]  F. D. Miller,et al.  Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain , 2000, Journal of neurochemistry.

[18]  D. Selkoe,et al.  Normal and abnormal biology of the beta-amyloid precursor protein. , 1994, Annual review of neuroscience.

[19]  A. Hofman,et al.  Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene , 1992, Nature Genetics.

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

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

[22]  M. Smith,et al.  Apolipoprotein E interaction with the neurofibrillary tangles and senile plaques in Alzheimer disease: implications for disease pathogenesis. , 1995, Biochemical and biophysical research communications.

[23]  E. Otomo,et al.  Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease , 1991, Brain Research.

[24]  J. Hardy,et al.  A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43). , 1997, Human molecular genetics.

[25]  D. Selkoe.  Alzheimer's disease: genes, proteins, and therapy. , 2001, Physiological reviews.

[26]  P. Southwick,et al.  Assessment of Amyloid β Protein in Cerebrospinal Fluid as an Aid in the Diagnosis of Alzheimer's Disease , 1996 .

[27]  J. Hardy,et al.  A locus for familial early–onset Alzhelmer's disease on the long arm of chromosome 14, proximal to the α1–antichymotrypsin gene , 1992, Nature Genetics.

[28]  M. Neumann,et al.  Decreased CSF amyloid β42 and normal tau levels in dementia with Lewy bodies , 2000, Neurology.

[29]  D. Campion,et al.  Unusual phenotypic alteration of β amyloid precursor protein (βAPP) maturation by a new Val-715 → Met βAPP-770 mutation responsible for probable early-onset Alzheimer’s disease , 1999 .

[30]  K. Blennow,et al.  Genetic testing for Alzheimer's disease: how close is reality? , 1999 .

[31]  R. Martins,et al.  A4 amyloid protein deposition and the diagnosis of Alzheimer's disease , 1988, Neurology.

[32]  J. Hardy,et al.  Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene , 1991, Nature.

[33]  K. Blennow,et al.  Development of a Specific Diagnostic Test for Measurement of β-Amyloid (1-42) [βA4(l-42)] in CSF , 1998 .

[34]  B. Ghetti,et al.  A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. , 1991, Science.

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

[36]  L. Thal,et al.  Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide , 1993, Nature.

[37]  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.

[38]  J. Hardy,et al.  Amyloid deposition as the central event in the aetiology of Alzheimer's disease. , 1991, Trends in pharmacological sciences.

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

[40]  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 .

[41]  K. Blennow,et al.  Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. , 2000, Journal of Alzheimer's disease : JAD.

[42]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[43]  E. Wolters,et al.  Concentrations of amyloid β protein in cerebrospinal fluid of patients with alzheimer's disease , 1995, Annals of neurology.

[44]  C. Cotman,et al.  Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[45]  K. Blennow,et al.  CSF levels of tau, β-amyloid1–42 and GAP-43 in frontotemporal dementia, other types of dementia and normal aging , 2000, Journal of Neural Transmission.

[46]  Pl Lantos,et al.  Greenfield's Neuropathology , 1985 .

[47]  E. Mandelkow,et al.  Tau in Alzheimer's disease. , 1998, Trends in cell biology.

[48]  K. Blennow,et al.  Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment , 1999, Neuroscience Letters.

[49]  L A Hansen,et al.  Clinical-neuropathological correlations in Alzheimer's disease and related dementias. , 1994, Archives of neurology.

[50]  P. Lansbury,et al.  The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. , 1993, Biochemistry.

[51]  D. Selkoe,et al.  Amyloid β-peptide is produced by cultured cells during normal metabolism , 1992, Nature.

[52]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[53]  Ruedi Aebersold,et al.  Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing , 2000, Nature.

[54]  H. Wiśniewski,et al.  Plasma amyloid β‐peptide 1–42 and incipient Alzheimer's disease , 1999 .

[55]  Robert J. Cotter,et al.  Elevated Aβ42 in Skeletal Muscle of Alzheimer Disease Patients Suggests Peripheral Alterations of AβPP Metabolism , 2000 .

[56]  R. Motter,et al.  Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse , 1999, Nature.

[57]  H. Wiśniewski,et al.  Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease , 1998, Neuroscience Letters.

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

[59]  M. Tabaton,et al.  Soluble amyloid beta-protein is a marker of Alzheimer amyloid in brain but not in cerebrospinal fluid. , 1994, Biochemical and biophysical research communications.

[60]  M. Emmerling,et al.  Amyloid and lipids in the pathology of Alzheimer disease. , 1999, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[61]  D. Selkoe,et al.  The Seminal Role of β‐Amyloid in the Pathogenesis of Alzheimer Disease , 1992 .

[62]  A. Fisher,et al.  Progress in Alzheimer’s and Parkinson’s Diseases , 1998, Advances in Behavioral Biology.

[63]  C. Masters,et al.  Serpents on the road to dementia and death , 1997, Nature Medicine.

[64]  C. Vigo‐Pelfrey,et al.  Rapid Communication: Characterization of β‐Amyloid Peptide from Human Cerebrospinal Fluid , 1993 .

[65]  T. Iwatsubo,et al.  Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43) , 1994, Neuron.

[66]  K. Beyreuther,et al.  Secretion of Alzheimer's disease Abeta amyloid peptide by activated human platelets. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[67]  S. Hirai,et al.  Amyloid β protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease , 1997, Journal of the Neurological Sciences.

[68]  E. Giacobini.  Cholinesterase Inhibitors Stabilize Alzheimer's Disease , 2000, Annals of the New York Academy of Sciences.

[69]  E. Kojro,et al.  Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[70]  G. Schellenberg,et al.  Candidate gene for the chromosome 1 familial Alzheimer's disease locus , 1995, Science.

[71]  C. Masters,et al.  Novel Leu723Pro amyloid precursor protein mutation increases amyloid β42(43) peptide levels and induces apoptosis , 2000, Annals of neurology.

[72]  W. Tourtellotte,et al.  Post-lumbar puncture headaches , 1964 .

[73]  Min Xu,et al.  Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1 , 2000, Nature.

[74]  B. Ghetti,et al.  Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. , 2000, Archives of neurology.

[75]  C. Patlak,et al.  Fate of Cerebrospinal Fluid‐Borne Amyloid β‐Peptide: Rapid Clearance into Blood and Appreciable Accumulation by Cerebral Arteries , 1996, Journal of neurochemistry.

[76]  D. Pollen,et al.  Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease , 1995, Nature.

[77]  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.

[78]  W. Snow,et al.  The NINCDS‐ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease , 1988, Neurology.

[79]  P. Mehta,et al.  The effects of age, apolipoprotein E phenotype and gender on the concentration of amyloid-β (Aβ) 40, Aβ42, apolipoprotein E and transthyretin in human cerebrospinal fluid , 1998 .

[80]  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.

[81]  K. Blennow,et al.  Standardization of measurement of β-amyloid(1-42) in cerebrospinal fluid and plasma , 2000, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[82]  J. Reed,et al.  Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's disease , 1991 .

[83]  J. Morris,et al.  Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease , 1999, Annals of neurology.

[84]  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.

[85]  G. Glenner,et al.  Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein , 1984 .

[86]  E. Oguni,et al.  Amyloid β protein in plasma from patients with sporadic Alzheimer's disease , 1996, Journal of the Neurological Sciences.

[87]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[88]  N. Suzuki,et al.  Biochemical evidence for the long-tail form (Aβ1-42/43) of amyloid β protein as a seed molecule in cerebral deposits of alzheimer′s disease , 1994 .

[89]  G. Getz,et al.  Isoform-specific binding of apolipoprotein E to beta-amyloid. , 1994, The Journal of biological chemistry.

[90]  D. Pollen,et al.  The genetic defect causing familial Alzheimer's disease maps on chromosome 21. , 1987, Science.

[91]  K. Blennow,et al.  Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. , 1999, Archives of neurology.

[92]  K. Davis,et al.  Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. , 2000, JAMA.

[93]  Thomas Wisniewski,et al.  Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid , 1992, Neuroscience Letters.

[94]  I. Lieberburg,et al.  Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. , 1990, Science.