Decreased vasopressin gene expression in the biological clock of Alzheimerdisease patients with and without depression

Circadian rhythm disturbances are frequently present in Alzheimer disease ( AD). In the present study, we investigated the expression of vasopressin (A VP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridizat ion procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA express ing neurons in the human SCN and carry out quantitative measurements. The t otal amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients (n = 14; 2,135 +/- 597 mu m(2)) than in age- and time-of-death-matched controls (n = 11; 6,667 +/- 1466 mu m(2)) (p = 0.003 ). No significant difference was found in the amount of AVP mRNA between AD patients with depression (n = 7) and without depression (n = 7) (2,985 +/- 1103 mu m(2) and 1.285 +/- 298 mu m2, respectively; p = 0.38). In addition , the human SCN AVP mRNA expressing neurons showed a marked day-night diffe rence in controls under 80 years of age. The amount of AVP mRNA was more th an 3 times higher during the daytime (9,028 +/- 1709 mu m(2), n = 7) than a t night (2,536 +/- 740 mu m(2). n = 4; p = 0.02), whereas no clear diurnal rhythm of AVP mRNA in the SCN was observed in AD patients. There was no rel ationship between the amount of AVP mRNA in the SCN and age at onset of dem entia, duration of AD and the neuropathological changes in the cerebral cor tex. These findings suggest that the neurobiological basis of the circadian rhythm disturbances that are responsible for behavioral rhythm disorders i s located in the SCN. It also explains the beneficial effects of light ther apy on nightly restlessness in AD patients.