Immunohistochemical Analysis of Cerebral Cortical and Vascular Lesions in the Primate Microcebus murinus Reveal Distinct Amyloid β1–42 and β1–40 Immunoreactivity Profiles

Recent reports have shown that amyloid beta deposits in the brains of Alzheimer's disease patients consist mainly of two distinct species of amyloid beta protein (Abeta) with different C-termini, Abeta1-42 (Abeta42) and Abeta1-40 (Abeta40). The nature of the Abeta species in Microcebus murinus brain was investigated immunocytochemically using polyclonal antibodies with clear specificity for the Abeta42 and Abeta40 C-termini. The cortical vascular deposits were immunopositive for both Abeta42 and Abeta40. However, most of the diffuse plaques were strongly positive for Abeta42 whereas only a subset of deposits were positive for Abeta40. Numerous cortical plaques were Abeta42-immunopositive but tested negative for Abeta40. This suggests that Abeta42 is probably associated with early stages of plaque maturation. This neuropathological feature reminiscent of that observed in brains affected by Alzheimer's disease further supports the idea that M. murinus could be used as a potential model of the early stages of this neurological disease.

[1]  M. Perret,et al.  Cloning of the Presenilin 2 cDNA and Its Distribution in Brain of the Primate,Microcebus murinus: Coexpression with βAPP and Tau Proteins , 1998, Neurobiology of Disease.

[2]  D. Albe-Fessard,et al.  A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus) , 1998, Brain Research Bulletin.

[3]  J. Buxbaum,et al.  Characterization of New Polyclonal Antibodies Specific for 40 and 42 Amino Acid-Long Amyloid β Peptides: Their Use to Examine the Cell Biology of Presenilins and the Immunohistochemistry of Sporadic Alzheimer’s Disease and Cerebral Amyloid Angiopathy Cases , 1997, Molecular medicine.

[4]  Y. Ihara,et al.  530 Amyloid β protein (Aβ) deposition in normal aging has the same characteristics as that in Alzheimer's disease: Predominance of Aβ42(43) and association of Aβ40 with cored plaques and microglial cells , 1996, Neurobiology of Aging.

[5]  A. Calenda,et al.  Molecular cloning, sequencing, and brain expression of the presenilin 1 gene in Microcebus murinus. , 1996, Biochemical and biophysical research communications.

[6]  Marla Gearing,et al.  Aβ 40 is a major form of β-amyloid in nonhuman primates , 1996, Neurobiology of Aging.

[7]  R. Veerhuis,et al.  The role of complement and activated microglia in the pathogenesis of Alzheimer's disease , 1996, Neurobiology of Aging.

[8]  T. Iwatsubo,et al.  Comparable amyloid β-protein (Aβ) 42(43) and Aβ40 deposition in the aged monkey brain , 1996, Neuroscience Letters.

[9]  S. M. Sumi,et al.  Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43) , 1996 .

[10]  Brian J Cummings,et al.  Diffuse plaques contain C-terminal Aβ 42 and not Aβ 40: Evidence from cats and dogs , 1996, Neurobiology of Aging.

[11]  A. Calenda,et al.  β-Amyloid Protein Precursor inMicrocebus murinus:Genotyping and Brain Localization , 1996, Neurobiology of Disease.

[12]  C. Hulette,et al.  Microglia Are Not Exclusively Associated with Plaque‐rich Regions of the Dentate Gyms in Alzheimer's Disease , 1996, Journal of neuropathology and experimental neurology.

[13]  J. Geddes,et al.  Age-specific onset of β-amyloid in Beagle brains , 1996, Neurobiology of Aging.

[14]  Kenneth H. Johnson,et al.  Aβ-Associated cerebral angiopathy and senile plaques with neurofibrillary tangles and cerebral hemorrhage in an aged wolverine (Gulo gulo) , 1996, Neurobiology of Aging.

[15]  H. Uno,et al.  Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques , 1996, Neurobiology of Aging.

[16]  H. Nakayama,et al.  A Retrospective Study of Canine Senile Plaques and Cerebral Amyloid Angiopathy , 1996, Veterinary pathology.

[17]  W. Markesbery,et al.  Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains , 1996, Neurobiology of Aging.

[18]  M. Lalowski,et al.  Amyloid beta 1-42 deposits do not lead to Alzheimer's neuritic plaques in aged dogs. , 1996, The Biochemical journal.

[19]  A. Calenda,et al.  Identification of a unique apolipoprotein E allele inMicrocebus murinus; apoe brain distribution and co-localization with β-amyloid and tau proteins , 1995, Neurobiology of Disease.

[20]  D. Mann,et al.  Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome , 1995, Annals of neurology.

[21]  H. Vinters,et al.  Polyclonals to β-amyloid(1–42) identify most plaque and vascular deposits in Alzheimer cortex, but not striatum , 1994, Brain Research.

[22]  H. Vinters,et al.  Monoclonal antibody to the C‐terminus of β‐amyloid , 1994 .

[23]  B T Hyman,et al.  Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[24]  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.

[25]  B T Hyman,et al.  Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys. , 1994, The American journal of pathology.

[26]  D. Selkoe,et al.  Identification of amyloid beta protein in the brain of the small, short-lived Lemurian primate Microcebus murinus , 1994, Neurobiology of Aging.

[27]  M J Ball,et al.  beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Okuda,et al.  Double-labeling immunohistochemical studies on canine senile plaques and cerebral amyloid angiopathy. , 1993, The Journal of veterinary medical science.

[29]  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.

[30]  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.

[31]  D. Selkoe,et al.  Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. , 1992, The Journal of biological chemistry.

[32]  N. Bons,et al.  Senile plaques and neurofibrillary changes in the brain of an aged lemurian primate, Microcebus murinus , 1992, Neurobiology of Aging.

[33]  D. Price,et al.  α1-Antichymotrypsin is present together with the β-protein in monkey brain amyloid deposits , 1989, Neuroscience.

[34]  D. Selkoe,et al.  Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease , 1989, Journal of Neuroimmunology.

[35]  D. Selkoe,et al.  Protein chemical and immunocytochemical studies of meningovascular β-amyloid protein in Alzheimer's disease and normal aging , 1988, Brain Research.

[36]  D. Price,et al.  Neurofibrillary Tangles and Senile Plaques in Aged Bears , 1988, Journal of neuropathology and experimental neurology.

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

[38]  D. Price,et al.  Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. , 1987, Science.

[39]  D. Price,et al.  Senile plaques in cortex of aged normal monkeys , 1985, Brain Research.

[40]  H. Wiśniewski,et al.  Neurofibrillary tangles of paired helical filaments , 1976, Journal of the Neurological Sciences.

[41]  H. Wiśniewski,et al.  NEURITIC (SENILE) PLAQUES AND FILAMENTOUS CHANGES IN AGED RHESUS MONKEYS , 1973, Journal of neuropathology and experimental neurology.

[42]  T. Iwatsubo,et al.  Amyloid beta protein deposition in normal aging has the same characteristics as that in Alzheimer's disease. Predominance of A beta 42(43) and association of A beta 40 with cored plaques. , 1996, The American journal of pathology.

[43]  S. Hirai,et al.  Immunohistochemical analysis of COOH-termini of amyloid beta protein (Aβ) using end-specific antisera for Aβ40 and Aβ42 in Alzheimer's disease and normal aging , 1995 .