Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease.
BACKGROUND
We evaluated the amounts of amyloid beta (Abeta)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on Abeta plasma levels and Alzheimer's disease (AD) pathology.


METHODS
Amyloid beta 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 Abeta 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 Abeta40 than disease-free vessels. Inactivated platelets contained more Abeta peptides than activated ones. Substantially more Abeta was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of Abeta.


CONCLUSIONS
Efforts to use plasma levels of Abeta 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 Abeta values is also due in part to the ability of Abeta 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 Abeta plasma levels. Furthermore, the long-range impact of Abeta immunotherapy on peripheral Abeta sources should also be considered.
Roher
Alex E
AE
The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, AZ, USA. alex.roher@bannerhealth.com
Esh
Chera L
CL
Kokjohn
Tyler A
TA
Castaño
Eduardo M
EM
Van Vickle
Gregory D
GD
Kalback
Walter M
WM
Patton
R Lyle
RL
Luehrs
Dean C
DC
Daugs
Ian D
ID
Kuo
Yu-Min
YM
Emmerling
Mark R
MR
Soares
Holly
H
Quinn
Joseph F
JF
Kaye
Jeffrey
J
Connor
Donald J
DJ
Silverberg
Nina B
NB
Adler
Charles H
CH
Seward
James D
JD
Beach
Thomas G
TG
Sabbagh
Marwan N
MN
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000378:metabolism; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008576:Meningeal Arteries / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002800:Cholinesterase Inhibitors