Cerebrospinal fluid from 39 healthy individuals showed evidence for increas
ing blood-CSF barrier permeability with age, and confirmed that haptoglobin
s are more sensitive but less predictive markers of barrier permeability th
an total protein. Haptoglobin (Hp) species were identified by polyacrylamid
e gel electrophoresis followed by immunoblotting. Hp 1-1 (35 Angstrom, 85 k
Da) was detected in all (9/9) subjects who exhibited this phenotype. Hp 2-1
(42 Angstrom, 120 kDa) was detected in 53% (8/15) of subjects in whom Hp 2
-1 was the phenotype. Hp 2-2 (54 Angstrom, 160 kDa) was detected in only 20
% (3/15) of subjects who exhibited this phenotype. The likelihood of detect
ing any haptoglobin species corresponded to the molecular size and the cons
equent resistance offered by the barrier. Among younger subjects aged less
than or equal to 45 years, a significant difference in incidence occurred b
etween the two smaller species Hp 1-1 and Hp 2-1. However, among those aged
>45, the significant difference in incidence was between the two larger sp
ecies Hp 2-1 and Hp 2-2. The incidence of detection among those with Hp 2-1
phenotypes was higher in the older age group. The increased likelihood of
detecting haptoglobins with age is in keeping with the notion that barrier
function is compromised by age, and also indicates that Hp 2-1 and Hp 2-2 a
re sensitive markers of barrier function. The appreciable incidence of hapt
oglobins in normal CSF, even of the larger species, suggests reservation in
assuming that their presence signifies barrier damage. (C) 2001 Elsevier S
cience B.V. All rights reserved.