BACKGROUND: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular mechanisms underlying synaptic degeneration are still unclear, and identifying abnormally expressed synaptic proteins in AD brain will help to elucidate such mechanisms and to identify therapeutic targets that might slow AD progression. METHODS: Synaptosomal fractions from human autopsy brain tissue from subjects with AD (n = 6) and without AD (n = 6) were compared using two-dimensional differential in-gel electrophoresis. AD pathology is region specific; human subjects can be highly variable in age, medication, and other factors. To counter these factors, two vulnerable areas (the hippocampus and the temporal cortex) were compared with two relatively spared areas (the motor and occipital cortices) within each group. Proteins exhibiting significant changes in expression were identified (≥20% change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption ionization time-of-flight or electrospray ionisation quadrupole-time of flight mass spectrometry. RESULTS: Twenty-six different synaptic proteins exhibited more than twofold differences in expression between AD and normal subjects. These proteins are involved in regulating different cellular functions, including energy metabolism, signal transduction, vesicle transport, structure, and antioxidant activity. CONCLUSION: Comparative proteome analysis uncovered markers of pathogenic mechanisms involved in synaptic dysfunction.
BACKGROUND: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular mechanisms underlying synaptic degeneration are still unclear, and identifying abnormally expressed synaptic proteins in AD brain will help to elucidate such mechanisms and to identify therapeutic targets that might slow AD progression. METHODS: Synaptosomal fractions from human autopsy brain tissue from subjects with AD (n = 6) and without AD (n = 6) were compared using two-dimensional differential in-gel electrophoresis. AD pathology is region specific; human subjects can be highly variable in age, medication, and other factors. To counter these factors, two vulnerable areas (the hippocampus and the temporal cortex) were compared with two relatively spared areas (the motor and occipital cortices) within each group. Proteins exhibiting significant changes in expression were identified (≥20% change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption ionization time-of-flight or electrospray ionisation quadrupole-time of flight mass spectrometry. RESULTS: Twenty-six different synaptic proteins exhibited more than twofold differences in expression between AD and normal subjects. These proteins are involved in regulating different cellular functions, including energy metabolism, signal transduction, vesicle transport, structure, and antioxidant activity. CONCLUSION: Comparative proteome analysis uncovered markers of pathogenic mechanisms involved in synaptic dysfunction.
Authors: Jessica L Hoffman; Sara Faccidomo; Michelle Kim; Seth M Taylor; Abigail E Agoglia; Ashley M May; Evan N Smith; L C Wong; Clyde W Hodge Journal: Int Rev Neurobiol Date: 2019-10-23 Impact factor: 3.230
Authors: M Domínguez-Álvaro; M Montero-Crespo; L Blazquez-Llorca; R Insausti; J DeFelipe; L Alonso-Nanclares Journal: Acta Neuropathol Commun Date: 2018-03-02 Impact factor: 7.801
Authors: Brian R Barnett; Fariba Fathi; Paulo Falco Cobra; Sue Y Yi; Jacqueline M Anderson; Hamid R Eghbalnia; John L Markley; John-Paul J Yu Journal: Metabolites Date: 2020-02-23
Authors: Àlex Bayés; Mark O Collins; Clare M Galtrey; Clémence Simonnet; Marcia Roy; Mike D R Croning; Gemma Gou; Louie N van de Lagemaat; David Milward; Ian R Whittle; Colin Smith; Jyoti S Choudhary; Seth G N Grant Journal: Mol Brain Date: 2014-11-28 Impact factor: 4.041