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Amyloid Plaque Deposition (amyloid + plaque_deposition)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Antibodies against ,-amyloid reduce a, oligomers, glycogen synthase kinase-3, activation and , phosphorylation in vivo and in vitro

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006
Qiu-Lan Ma
Abstract Although active and passive immunization against the ,-amyloid peptide (A,) of amyloid plaque-bearing transgenic mice markedly reduces amyloid plaque deposition and improves cognition, the mechanisms of neuroprotection and impact on toxic oligomer species are not understood. We demonstrate that compared to control IgG2b, passive immunization with intracerebroventricular (icv) anti-A, (1,15) antibody into the AD HuAPPsw (Tg2576) transgenic mouse model reduced specific oligomeric forms of A,, including the dodecamers that correlate with cognitive decline. Interestingly, the reduction of soluble A, oligomers, but not insoluble A,, significantly correlated with reduced , phosphorylation by glycogen synthase kinase-3, (GSK-3,), a major , kinase implicated previously in mediating A, toxicity. A conformationally-directed antibody against amyloid oligomers (larger than tetramer) also reduced A, oligomer-induced activation of GSK3, and protected human neuronal SH-SY5Y cells from A, oligomer-induced neurotoxicity, supporting a role for A, oligomers in human , kinase activation. These data suggest that antibodies that are highly specific for toxic oligomer subspecies may reduce toxicity via reduction of GSK-3,, which could be an important strategy for Alzheimer's disease (AD) therapeutics. © 2005 Wiley-Liss, Inc. [source]

Visualization of ,-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents

MAGNETIC RESONANCE IN MEDICINE, Issue 3 2004
Sang-Pil Lee
Abstract The visualization of ,-amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, ,-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. ,-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for ,-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of ,-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging. Magn Reson Med 52:538,544, 2004. © 2004 Wiley-Liss, Inc. [source]

Familial British dementia (FBD): a cerebral amyloidosis with systemic amyloid deposition

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002
J. L. Holton
Introduction:, FBD is an autosomal dominant disease with neuropathological similarities to Alzheimer's disease (AD) as it is characterized by amyloid angiopathy, parenchymal amyloid plaque deposition and neurofibrillary degeneration. FBD is associated with a stop codon mutation in the BRI2 gene encoding a type II transmembrane protein, BriPP. Mutation results in an extended precursor protein, ABriPP, from which a C-terminal 34 amino acid peptide (ABri) is generated by furin-like proteolytic cleavage and deposited as amyloid and preamyloid in the central nervous system. Despite the morphological parallels with AD the sequences of the amyloidogenic peptides, ABri in FBD and A, in AD, are completely different. We examined systemic tissues in FBD for ABri deposition. Materials and methods:, Immunohistochemistry using an ABri-specific antibody, Ab338, counterstained with Thioflavin S and Ab338 immuno-electron microscopy identified ABri deposits and determined whether these were amyloid or preamyloid in nature. Results:, Amyloid bearing blood vessels stained positively for ABri in myocardium, uterus, bladder, spleen, pancreas, lung and skeletal muscle. ABri was also identified in either amyloid or preamyloid conformation in the parenchyma of myocardium, adrenal, pancreas and skeletal muscle. Conclusion:, This study demonstrates that FBD is the first described cerebral amyloidosis with neurofibrillary pathology and dementia to be accompanied by systemic amyloid deposition. [source]

Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2007
Frank Gillardon Dr.
Abstract Synaptic dysfunction is an early event in Alzheimer's disease patients and has also been detected in transgenic mouse models. In the present study, we analyzed proteomic changes in synaptosomal fractions from Tg2576 mice that overexpress mutant human amyloid precursor protein (K670N, M671L) and from their nontransgenic littermates. Cortical and hippocampal tissue was microdissected at the onset of cognitive impairment, but before deposition of amyloid plaques. Crude synaptosomal fractions were prepared by differential centrifugation, proteins were separated by 2-D DIGE and identified by MS/MS. Significant alterations were detected in mitochondrial heat shock protein 70 pointing to a mitochondrial stress response. Subsequently, synaptosomal versus nonsynaptic mitochondria were purified from Tg2576 mice brains by density gradient centrifugation. Mitochondrial proteins were separated by IEF or Blue-native gel electrophoresis in the first dimension and SDS-PAGE in the second dimension. Numerous changes in the protein subunit composition of the respiratory chain complexes I and III were identified. Levels of corresponding mRNAs remain unchanged as shown by Affymetrix oligonucleotide array analysis. Functional examination revealed impaired state 3 respiration and uncoupled respiration in brain mitochondria from young Tg2576 mice. By immunoblotting, amyloid-beta oligomers were detected in synaptosomal fractions from Tg2576 mice and reduced glucose metabolism was observed in Tg2576 mice brains by [14C]-2-deoxyglucose infusion. Taken together, we demonstrate alterations in the mitochondrial proteome and function that occur in Tg2576 mice brains before amyloid plaque deposition suggesting that mitochondria are early targets of amyloid-beta aggregates. [source]