Sir: Urinary neopterin:biopterin ratios are elevated in senile dementia
of the Alzheimer type (SDAT) compared with age matched controls, due to a
reduced conversion of dihydroneopterin triphosphate to tetra-hydrobiopterin.[1,
2] There is a similar elevated neopterin:biopterin ratio in Down's syn-drome, a
condition producing a similar dementia to SDAT.
Morning urines were collected into ascor-bic acid (2% final
concentration) from a group of 53 Downs sufferers of mixed sex aged between 1
to 70 years without any other disease and, following storage at - 20°C, the
neopterin and biopterin levels were determined by HPLC after acid iodine
oxidation [3]. Compared with a group of 35 healthy con-trols of mixed sex and
aged 23 to 93 years, the neopterin:biopterin ratio was significantly elevated
3.44, 1.73 vs 1.12, 0.55 (mean, SD) p < 0.2% (table). Against a creatinine
baseline biopterin levels were unaffected but the urin-ary neopterin levels
were significantly increased (Table). No age trend was observed suggesting that
these metabolic effects precede dementia onset. The elevated
neopterin:biopterin ratio could be due to a disease related immune response
causing stimulation of neopterin biosynthesis,[4] alth-ough all disease states
known to produce such were absent and the rise is less pronoun-ced that in such
conditions. It is known that there are disturbances in the immune system of
Down's patients, [5] and it could be sugges-ted that these disturbances are
causing the rise in urinary neopterin in a similar manner to viral and
malignant disorders. However, it has been found that interferon gamma (IFNg)
production is lower in Down's patients than in normal patients with
infec-tion.[6] It is IFNg which stimulates the macrophages to produce neopterin
in infectious disorders,[7] so any decrease in IFNg levels should result in
similar or reduced levels of urinary neopterin and not the increased levels
observed. A second possibility is the presence of greater levels of guanosinc
triphosphate in the purine pool from an increased biosynthesis of purines as a
result of the extra chromosome 21, which has the locus for some of the enzymes
for purine biosynthesis.
The levels of neopterin and biopterin are measured against a creatinine
baseline. In the Downs subjects creatinine clearance is repor-tedly lower,
reflecting a reduced glomerular nitration rate,[8] and this could be causing a
distortion in the results. However, creatinine clearance has a positive linear
correlation with both neopterin and biopterin[9] so any reduction in the
baseline will be compensated for by reduced pterin excretion. This would also
account for the elevated levels of biopterins in the plasma of such
subjects.[10]
There is a greater incidence of Alzheimer type changes in Down's
syndrome patients than in the normal population,[11] and Down's syndrome has
been suggested as a model for accelerated ageing.[12) However, there is no
correlation between age and urinary N/B ratio in Down's syndrome from birth and
not one acquired with age.
Table Neopterin and biopterin levels in Down's subjects and
healthy controls
| N | Neopterin/Creatinine (mean,
SD) | Biopterin/Creatinine (mean, SD) | Creatinine (mmol/l) (mean,
SD) | N:B (mean, SD) |
Downs syndrome | 53 | 0.47, 0.32 | 0.17,
0.14 | 8.22, 5.3 | 3.44, 1.7 |
Control | 32 | 0.14, 0.17 | 0.11,
0.1 | 12.3, 11.8 | 1.12; 0.55 |
P | | < 0.2
% | NS | NS | < 0.2 % |
Units µmol pteridine /mmol crealinine. |
Haut
References
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