We read with interest the hypothesis by McCaddon et
al [1] in which oxidative stress discussed underlying moderate
hyperhomocysteinemia in AD. It is suggested that
the oxidation-sensitive intermediate form of vitamin B12
(cob[I]alamin) will be destroyed thereby impairing remethylation of
homocysteine and giving rise to moderate hyperhomocysteinemia. The authors
further speculate that cerebral oxidative stress plays a major role. These
assumptions confirm our findings that oxidative stress may underlie moderate hyperhomocysteinemia. [2,3]
Not only the intermediate form of vitamin B12 but also methyl-
tetrahydrofolate, the second necessary cofactor in the remethylation of
homocysteine, is very sensitive to oxidation and as a 6-substituted
pteridinederivative is irreversibly degraded once oxidized. This may impact other clinical conditions such as
atherosclerosis, depression and even cancer, [2-4] which are often associated
with moderate hyperhomocysteinemia.
Interestingly, folate deficiency is detected more often in patients than vitamin B12 deficiency,
further supporting the concept that also degradation of folate is
important.
The results confirm a state of chronic immune activation in
patients with AD. [5] Homocysteine concentrations
correlate with the degree of immune activation as measured by, for example,
neopterin concentrations. [3] This association is also found in other
clinical conditions with hyperhomocysteinemia. [3,4] Activation of
immunocompetent cells like T-lymphocytes and macrophages is associated
with the production of large amounts of oxidizing compounds, indicating
oxidative stress. The immunopathogenetic background of
oxidative stress resulting in vitamin depletion and thus
hyperhomocysteinemia is likely and would confirm the
concept proposed by McCadden et al.
References
1. McCaddon A, Regland B, Hudson P, Davies G. Functional vitamin B(12)
deficiency and Alzheimer disease. Neurology 2002;58:1395-9.
2. Widner B, Fuchs D, Leblhuber F, Sperner-Unterweger B. Does disturbed
homocysteine and folate metabolism in depression result from enhanced
oxidative stress? J Neurol Neurosurg Psych 2001;70:419.
3. Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber
F. Is hyperhomocysteinemia due to oxidative depletion of folate rather
than insufficient dietary intake. Clin Chem Lab Med 2001;39:691-4.
4. Frick B, Schröcksnadel K, Fuchs D. Folate and homocysteine levels in
head and neck squamous cell carcinoma. Cancer (in press).
5. Leblhuber F, Walli J, Demel U, Tilz GP, Widner B, Fuchs D: Increased
serum neopterin concentrations in patients with Alzheimer's disease. Clin
Chem Lab Med 1999;37: 429-31.
We read with interest the hypothesis by McCaddon et al [1] in which oxidative stress discussed underlying moderate hyperhomocysteinemia in AD. It is suggested that the oxidation-sensitive intermediate form of vitamin B12 (cob[I]alamin) will be destroyed thereby impairing remethylation of homocysteine and giving rise to moderate hyperhomocysteinemia. The authors further speculate that cerebral oxidative stress plays a major role. These assumptions confirm our findings that oxidative stress may underlie moderate hyperhomocysteinemia. [2,3]
Not only the intermediate form of vitamin B12 but also methyl- tetrahydrofolate, the second necessary cofactor in the remethylation of homocysteine, is very sensitive to oxidation and as a 6-substituted pteridinederivative is irreversibly degraded once oxidized. This may impact other clinical conditions such as atherosclerosis, depression and even cancer, [2-4] which are often associated with moderate hyperhomocysteinemia.
Interestingly, folate deficiency is detected more often in patients than vitamin B12 deficiency, further supporting the concept that also degradation of folate is important. The results confirm a state of chronic immune activation in patients with AD. [5] Homocysteine concentrations correlate with the degree of immune activation as measured by, for example, neopterin concentrations. [3] This association is also found in other clinical conditions with hyperhomocysteinemia. [3,4] Activation of immunocompetent cells like T-lymphocytes and macrophages is associated with the production of large amounts of oxidizing compounds, indicating oxidative stress. The immunopathogenetic background of oxidative stress resulting in vitamin depletion and thus hyperhomocysteinemia is likely and would confirm the concept proposed by McCadden et al.
References
1. McCaddon A, Regland B, Hudson P, Davies G. Functional vitamin B(12) deficiency and Alzheimer disease. Neurology 2002;58:1395-9.
2. Widner B, Fuchs D, Leblhuber F, Sperner-Unterweger B. Does disturbed homocysteine and folate metabolism in depression result from enhanced oxidative stress? J Neurol Neurosurg Psych 2001;70:419.
3. Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber F. Is hyperhomocysteinemia due to oxidative depletion of folate rather than insufficient dietary intake. Clin Chem Lab Med 2001;39:691-4.
4. Frick B, Schröcksnadel K, Fuchs D. Folate and homocysteine levels in head and neck squamous cell carcinoma. Cancer (in press).
5. Leblhuber F, Walli J, Demel U, Tilz GP, Widner B, Fuchs D: Increased serum neopterin concentrations in patients with Alzheimer's disease. Clin Chem Lab Med 1999;37: 429-31.