Neurology 2002;58:1395-1399
© 2002 American Academy of Neurology
Medical Hypothesis
Functional vitamin B12 deficiency and Alzheimer disease
A. McCaddon, MRCGP,
B. Regland, MD PhD,
P. Hudson, MSc and
G. Davies, MSc
From the University of Wales College of Medicine (Dr. McCaddon), Division of General Practice, Wrexham, UK; Institute of Clinical Neuroscience (Dr. Regland), Psychiatry Section, Göteborg University, Sweden; and Biochemistry Department (P. Hudson and G. Davies), Wrexham Maelor Hospital, North Wales, United Kingdom.
Address correspondence and reprint requests to Dr. A. McCaddon, Gardden Road Surgery, Rhosllanerchrugog, Wrexham LL14 2EN, UK; e-mail: andrew{at}mccaddon.demon.co.uk
Moderately elevated total serum homocysteine is associated with an increased risk of atherothrombotic vascular events. Accordingly, serum homocysteine is increased in patients with vascular dementia but is also increased in clinically diagnosed and histologically confirmed AD. It is generally considered that homocysteine potentiates endothelial and neuronal oxidative injury in these diseases. A complementary model of oxidative stress–induced hyperhomocystinemia is proposed by the authors. The hypothesis accounts for several unusual features relating to single-carbon metabolism and AD, including the absence of macrocytic anemia in these patients. It is suggested that cerebral oxidative stress augments the oxidation of an intermediate form of vitamin B12 (cob[I]alamin) generated in the methionine synthase reaction, thereby impairing the metabolism of homocysteine. Oxidative stress also compromises the intraneuronal reduction of the vitamin to its metabolically active state. Currently available pharmaceutic forms of vitamin B12 are unlikely to be utilized by neurons under these conditions. Glutathionylcobalamin might be preferential for the treatment of such patients.
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Correspondence:
Read all Correspondence
- Functional vitamin B12 deficiency and Alzheimer disease
- Dietmar Fuchs, et al.
- Neurology Online, 12 Sep 2002
[Full text]
- Reply to Fuchs
- Andrew McCaddon, et al.
- Neurology Online, 30 Sep 2002
[Full text]
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