Norepinephrine and MHPG Levels in CSF and Plasma in Alzheimer's Disease

Postmortem findings of decreased brain norepinephrine (NE) content and decreased locus ceruleus neuronal density have suggested a possible noradrenergic deficit in Alzheimer's disease (AD). We assessed CNS and peripheral noradrenergic function in patients with advanced AD, moderate AD, and age-matched normals by measuring NE and the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in CSF and plasma. Subjects were drug free for at least two weeks. Plasma and CSF NE and MHPG levels were significantly higher in patients with advanced AD than in either patients with moderate AD or normal controls, while values in the patients with moderate AD did not differ from those in normal controls. These findings do not support either a central or peripheral noradrenergic deficit in AD. Rather, they suggest increased CNS and peripheral noradrenergic activity in advanced stages of the disease.