Alzheimer disease (AD) is an age-related neurological disor- der that leads to progressive dementia and is characterized by the presence of ?-Amyloid (A?) plaques in the brain. The pathogenesis of AD is unclear, and it is controversial whether AD results from a primary abnormality in amyloid precursor protein (APP) or deregulation of the inflammatory system, although these two possibilities are not mutually exclusive.The definitive diagnosis of AD is based on both the observation of senile plaques and neurofibrillary tangles.The objective of the present study was to analyze A?-specific T-cell responses in patients suffering from AD.T-cell infiltrates in AD lesions have been described and mechanisms of T cell transendothelial migration have been suggested. A role of T-cells in progressing AD is being discussed. Here we describe for the first time the detection and functional analysis of A?-specific T-cell in blood from Alzheimer patients. Using 9-colour flow-cytometry we were able to detect A?-specific T-cell responses in peripheral blood of AD patients but not age-matched controls. A?-specif- ic T-cells were analysed in regards of T-cell lineage, cytokine production and expression of P-PKCs.They were found to show an activation pattern characterized by bright levels of P-PKC-? and P-PKC-? and a skewed profile of cytokine pro- duction. While these results are a major advance in under- standing the T-cell response to A?, the exact role of T-cells in AD will have to be addressed in future studies.

A POSSIBLE APPROACH TO THE EARLY DIAGNOSIS OF ALZHEIMER'S DISEASE BY FLOW CYTOMETRIC ANALYSIS OF T LYMPHOCYTES

MA Centurione;
2009

Abstract

Alzheimer disease (AD) is an age-related neurological disor- der that leads to progressive dementia and is characterized by the presence of ?-Amyloid (A?) plaques in the brain. The pathogenesis of AD is unclear, and it is controversial whether AD results from a primary abnormality in amyloid precursor protein (APP) or deregulation of the inflammatory system, although these two possibilities are not mutually exclusive.The definitive diagnosis of AD is based on both the observation of senile plaques and neurofibrillary tangles.The objective of the present study was to analyze A?-specific T-cell responses in patients suffering from AD.T-cell infiltrates in AD lesions have been described and mechanisms of T cell transendothelial migration have been suggested. A role of T-cells in progressing AD is being discussed. Here we describe for the first time the detection and functional analysis of A?-specific T-cell in blood from Alzheimer patients. Using 9-colour flow-cytometry we were able to detect A?-specific T-cell responses in peripheral blood of AD patients but not age-matched controls. A?-specif- ic T-cells were analysed in regards of T-cell lineage, cytokine production and expression of P-PKCs.They were found to show an activation pattern characterized by bright levels of P-PKC-? and P-PKC-? and a skewed profile of cytokine pro- duction. While these results are a major advance in under- standing the T-cell response to A?, the exact role of T-cells in AD will have to be addressed in future studies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/7661
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