Conversion of brain apolipoprotein E to an insoluble form in a mouse model of Alzheimer disease

Aβ deposition in the APPV717F transgenic model of Alzheimer's pathology involves apolipoprotein E (apoE). We measured soluble and insoluble apoE in brain region extracts at an early and late stage of plaque development. The apoE levels in the insoluble fraction were greatly elevated in the hippocampus and cortex of aged transgenic animals but were unchanged in wild type or young APPV717F animals. Soluble apoE levels were unaltered. Aβ levels were also measured and a positive correlation between apoE and Aβ in the insoluble fraction was observed. ApoE transcription was increased ∼3-fold in the hippocampus of 17-month-old APPV717F mice, suggesting a region-specific upregulation of apoE transcription in the brains of APPV717F mice to compensate for apoE sequestered with fibrillar Aβ.

[1]  D. Sanan,et al.  Isolation and Characterization of Apolipoproteins from Murine Microglia , 2000, The Journal of Biological Chemistry.

[2]  D. Holtzman,et al.  Neuroinflammation and Alzheimer’s disease: critical roles for cytokine/Aβ-induced glial activation, NF-κB, and apolipoprotein E , 2000, Neurobiology of Aging.

[3]  S. Paul,et al.  Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Trojanowski,et al.  The Levels of Soluble versus Insoluble Brain Aβ Distinguish Alzheimer's Disease from Normal and Pathologic Aging , 1999, Experimental Neurology.

[5]  M. Tabaton,et al.  Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. DeKosky,et al.  Expression of differential immune factors in temporal cortex and cerebellum: The role of α‐1‐antichymotrypsin, apolipoprotein E, and reactive glia in the progression of Alzheimer's disease , 1998, The Journal of comparative neurology.

[7]  W. Griffin,et al.  Glial‐Neuronal Interactions in Alzheimer's Disease: The Potential Role of a ‘Cytokine Cycle’ in Disease Progression , 1998, Brain pathology.

[8]  B. Permanne,et al.  Detection of apolipoprotein E/dimeric soluble amyloid beta complexes in Alzheimer's disease brain supernatants. , 1997, Biochemical and biophysical research communications.

[9]  B. Sommer,et al.  Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Paul,et al.  Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition , 1997, Nature Genetics.

[11]  R. Motter,et al.  Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse model of Alzheimer disease , 1997 .

[12]  D. Selkoe,et al.  Alzheimer's Disease--Genotypes, Phenotype, and Treatments , 1997, Science.

[13]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.

[14]  W. Griffin,et al.  Apolipoprotein E distribution among different plaque types in Alzheimer's disease: implications for its role in plaque progression , 1996, Neuropathology and applied neurobiology.

[15]  M. Gearing,et al.  Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease , 1996 .

[16]  K Kontula,et al.  Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. , 1995, The New England journal of medicine.

[17]  G. Schellenberg,et al.  Genetic dissection of Alzheimer disease, a heterogeneous disorder. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Wernstedt,et al.  Characterization of stable complexes involving apolipoprotein E and the amyloid β peptide in Alzheimer's disease brain , 1995, Neuron.

[19]  A D Roses,et al.  Apolipoprotein E and Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  L. Mucke,et al.  Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein , 1995, Nature.

[21]  H. Brewer,et al.  Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments , 1994, Nature.

[22]  T Vogel,et al.  Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. , 1994, The American journal of pathology.

[23]  A D Roses,et al.  Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  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.

[25]  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.