Amyloid-beta peptides in human plasma and tissues and their significance for Alzheimer's disease

ROHER AE; ESH CL; CASTAÑO EM; VAN VICKLE G; KALBACK WM; PATTON RL; LUEHRS DC; DAUGS ID; KUO YM; EMMERLING MR; SOARES H, ; QUINN JF; KAYE J, ; CONNOR DJ; SILVERBERG NB; ADLER CH; SEWARD JD; BEACH TG; SABBAGH MN

ALZHEIMERS & DEMENTIA

ELSEVIER SCIENCE INC

Año: 2009 vol. 5 p. 18 - 29

1552-5260

Background: We evaluated the amounts of amyloid beta (Ab)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Ab plasma levels and Alzheimer¡¦s disease (AD) pathology. Alzheimer¡¦s disease (AD) pathology. (CNS) and in reservoirs outside the CNS and their potential impact on Ab plasma levels and Alzheimer¡¦s disease (AD) pathology. Alzheimer¡¦s disease (AD) pathology. We evaluated the amounts of amyloid beta (Ab)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Ab plasma levels and Alzheimer¡¦s disease (AD) pathology. Alzheimer¡¦s disease (AD) pathology. b plasma levels and Alzheimer¡¦s disease (AD) pathology. Methods: Amyloid b levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. Amyloid b levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. Results: Plasma Ab levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of Ab40 than disease-free vessels. Inactivated platelets contained more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of Ab40 than disease-free vessels. Inactivated platelets contained more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. Plasma Ab levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of Ab40 than disease-free vessels. Inactivated platelets contained more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. b40 than disease-free vessels. Inactivated platelets contained more Ab peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab. b peptides than activated ones. Substantially more Ab was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Ab.b. Conclusions: Efforts to use plasma levels of Ab peptides as AD biomarkers or disease-staging scales have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma Ab values is also due in part to the ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma Ab values is also due in part to the ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. Efforts to use plasma levels of Ab peptides as AD biomarkers or disease-staging scales have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma Ab values is also due in part to the ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. b values is also due in part to the ability of Ab to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. b to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring Ab plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered. Ab sources should also be considered. b plasma levels. Furthermore, the long-range impact of Ab immunotherapy on peripheral Ab sources should also be considered.b sources should also be considered. 2009 The Alzheimer¡¦s Association. All rights reserved2009 The Alzheimer¡¦s Association. All rights reserved