Lipoprotein‐free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome

Abstract

About 90% of the soluble amyloid beta (sA beta) that circulates in normal human plasma is associated with lipoprotein particles. In sporadic Alzheimer's disease patients, free sA beta42 but not sA beta40 is increased approximately 2.3-fold compared with age-matched controls, although a more marked elevation (approximately 8-fold for free sA beta40 and about 20-fold for sA beta42) is found in Down's syndrome patients. The data suggest that lipoprotein-sA beta dissociation may contribute to the influx of sA beta into the brain as a result of decreased plasma clearance.

Progranulin protein levels are differently regulated in plasma and CSF

“…While plasma and CSF PGRN levels were similarly influenced by age, with an increase of approximately 2% to 3% per 5 years, opposing effects were observed when our cohort was stratified by sex, with male participants showing significant 7% lower levels of PGRN in plasma but 5% higher levels of PGRN in CSF as compared with female participants. [14][15][16][17][18][19][20] Other elements, including genetic modifiers, epigenetic aspects, epidemiologic influences, and/or environmental factors, are also likely to influence PGRN levels. None of these factors significantly affected PGRN in either plasma or CSF.…”

Dissociation of β-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates β-amyloid-42 assembly

“…We hypothesized that an alteration of the lipoprotein–sAβ interaction in the CNS is capable of initiating and/or accelerating the cascade favoring Aβ assembly. Actually, we demonstrate that functionally declined lipoproteins may be the major determinants in the generation of metabolic conditions leading to higher levels of the soluble dimeric form of Aβ in AD brains (Matsubara et al,1999,2004). To verify this hypothesis and extend previous observations (Matsubara et al,1999,2004), we focused on the entorrhinal cortex (EC) as well as CSF, which mimics CNS environments, followed by biochemical analyses using an antioligomer specific antibody.…”

Aging and APOE‐ε4 are determinative factors of plasma Aβ42 levels

“…Sandwich ELISA was used to quantify plasma A β x‐40 and A β x‐42 levels using a Human/Rat β Amyloid (40) ELISA Kit Wako II and a Human/Rat β Amyloid (42) ELISA Kit Wako High‐Sensitive (Wako Pure Chemical Industries, Ltd, Osaka, Japan) 22, 23. Microplates were precoated with monoclonal BNT77 (IgA, anti‐A β 11‐28, specific for A β 11‐16) and sequentially incubated with 25  μ L of samples, followed by application of horseradish‐peroxidase‐conjugated BA27 (anti‐A β 1‐40, specific for A β 40) or BC05 (anti‐A β 35‐43, specific for A β 42/43).…”