Thyroid stimulating hormone - Receptor overexpression in brain of patientswith Down Syndrome and Alzheimer's disease

Thyroid hormone abnormalities are strongly associated with Down Syndrome (D S) with elevated thyroid stimulating hormone (TSH) levels as the most consi stent finding. Using subtractive hybridization for gene hunting we found si gnificant overexpression of mRNA levels for the TSH-receptor (TSH-R) in bra in of a fetus with DS. Based upon this observation we determined TSH-R prot ein levels in five brain regions of patients with DS(n=8), Alzheimer diseas e(AD, n=8) and controls (C, n=8). Western blots revealed significantly elev ated immunoreactive TSH-R protein(s) 40 kD and 61kD in temporal and frontal cortex of patients with DS and, unexpectedly, in AD. Levels for the 40kD p rotein in temporal cortex were 1.00+/-0.036 (arbitrary units+/-SD) in C, 1. 35+/-0.143 in DS, 1.52+/-0.128 in AD; in frontal cortex: 1.00+/-0.046 in C, 1.10+/-0.03 in DS, 1.10+/-0.038 in AD. Levels for the 61kD protein in temp oral cortex were 1.01+/-0.015 in C, 1.47+/-0.013 in DS, 1.623+/-0.026 in AD ; in frontal cortex: 1.02+/-0.020 in C, 1.18 +/-0.123 in DS, 1.48+/-0.020 i n AD. These results show that elevated brain immunoreactive TSH-R is not sp ecific for DS and maybe reflecting apoptosis, a hallmark of both neurodegen erative disorders, as it is well-documented that the thyroid hormone system is involved in the control of programmed cell death.