Brain Support

Several studies indicate that a Central Nervous System (CNS) methyl group deficiency may play a role in the etiology of Alzheimer disease (AD). Reduced SAMe concentrations were found in Cerebrosipinal Spinal Fluid (CSF) (34) and in several different brain regions (51) of patients with AD. In addition, reduced phosphatidylcholine concentrations were found in postmortem brain tissue from AD patients (52), and significant changes in brain phospholipids that are dependent on SAMe metabolism were detected in vivo with 31p magnetic resonance spectroscopy in the early stages of AD (53). Deficiencies of folate and vitamin B-12 are common in the elderly (39, 40) and can lead to decreased CNS SAMe concentrations. Several studies indicate that elevated blood homocysteine concentrations, considered to be a marker for folate deficiency, vitamin B-12 deficiency, and impaired methylation, may be a risk factor for AD (54–56). It is therefore important to note that preliminary studies using either SAMe (57) or alternative methyl group donors [such as betaine (58) or folate and vitamin B-12 (59, 60)] can support cognitive function. These therapeutic regimens may be able to restore methyl group metabolism and normalize blood homocysteine concentrations. Reduced SAMe concentrations in CSF were also reported in patients with subacute combined degeneration of the spinal cord resulting from folate or vitamin B-12 deficiency (39) and in children with inborn errors of the methyl-transfer pathway who had demyelination (61). In these cases,therapeutic benefits with methyl-group donors such as SAMe, methyltetrahydrofolate, betaine, and methionine was associated with remyelination and a clinical response (61).

In three independent studies, reduced SAMe concentrations in CSF were found in HIV-infected patients; one study was conducted in children (62) and the other two studies were conducted in adults (35, 63). Although the cause of the decreased CSF SAMe concentrations in HIV infection is unknown, it was hypothesized that the resulting methyl-group deficiency may be a pathogenic mechanism involved in the etiology of the vacuolar myelopathy that is often part of the AIDS dementia complex (64). Furthermore, HIV-related vacuolar myelopathy bears a striking histologic resemblance to subacute combined degeneration of the spinal cord, which can accompany folate and vitamin B-12 deficiencies (65). Contrary to the studies discussed above, Goggins et al (66) reported that the amount of radiolabelled SAM incorporated into carboxymethyl and N-methylation sites within brain proteins from cortical white matter in vitro was significantly lower in samples from nine HIV-positive patients than in samples from sixteen control subjects; only four of the nine patients had HIV encephalitis. These data suggest that cortical brain proteins are hypermethylated in HIV-positive patients.