Thyroid stimulating hormone-receptor overexpression in brain of patients with Down syndrome and Alzheimer's disease

Topic: Brain proteins, microglia and lab models

Thyroid hormone abnormalities are strongly associated with Down Syndrome (DS) with elevated thyroid stimulating hormone (TSH) levels as the most consistent finding. Using subtractive hybridization for gene hunting we found significant overexpression of mRNA levels for the TSH-receptor (TSH-R) in brain of a fetus with DS. Based upon this observation we determined TSH-R protein levels in five brain regions of patients with DS (n=8), Alzheimer disease (AD, n=8) and controls (C, n=8). Western blots revealed significantly elevated immunoreactive TSH-R protein(s) 40 kD and 61 kD in temporal and frontal cortex of patients with DS and, unexpectedly, in AD. Levels for the 40 kD protein 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 61 kD protein in temporal 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 in AD. These results show that elevated brain immunoreactive TSH-R is not specific for DS and maybe reflecting apoptosis, a hallmark of both neurodegenerative disorders, as it is well-documented that the thyroid hormone system is involved in the control of programmed cell death.

@article{labudova1999-10210286,
  author  = {Labudova, O. and Cairns, N. and Koeck, T. and Kitzmueller, E. and Rink, H. and Lubec, G.},
  title   = {{Thyroid stimulating hormone-receptor overexpression in brain of patients with Down syndrome and Alzheimer's disease}},
  journal = {Life sciences},
  year    = {1999},
  doi     = {10.1016/s0024-3205(99)00030-2},
  pmid    = {10210286},
  url     = {https://doi.org/10.1016/s0024-3205(99)00030-2}
}

Key findings

• Thyroid hormone abnormalities are strongly associated with Down Syndrome (DS) with elevated thyroid stimulating hormone (TSH) levels as the most consistent finding.
• Using subtractive hybridization for gene hunting we found significant overexpression of mRNA levels for the TSH-receptor (TSH-R) in brain of a fetus with DS.
• Western blots revealed significantly elevated immunoreactive TSH-R protein(s) 40 kD and 61 kD in temporal and frontal cortex of patients with DS and, unexpectedly, in AD.
• These results show that elevated brain immunoreactive TSH-R is not specific for DS and maybe reflecting apoptosis, a hallmark of both neurodegenerative disorders, as it is well-documented that the thyroid hormone system is involved in the control of programmed cell death.

Why it matters

This study found elevated levels of the TSH-receptor protein in brain regions of people with Down syndrome and, unexpectedly, Alzheimer's disease. The finding was not specific to Down syndrome and the authors suggest it may reflect apoptosis, so it does not provide a treatment or prevention approach.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0024-3205(99)00030-2
• PubMed: 10210286
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Evidence against increased oxidative DNA-damage in Down syndrome Neuroscience letters · 1997-10-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Autoimmune thyroiditis associated with mild "subclinical" hypothyroidism in adults with Down syndrome: a comparison of patients with and without manifestations of Alzheimer disease American journal of medical genetics · 1990-06-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

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• Decreased cyclin dependent kinase in brain of patients with Down syndrome Neuroscience letters · 1996-09-01 · usefulness score 35/100
• Brain atrophy in 18 patients with Down syndrome: a CT study AJNR. American journal of neuroradiology · 1990-07-01 · usefulness score 33/100
• Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2002-07-01 · usefulness score 32/100
• The glutamatergic hypothesis for Down syndrome: the potential use of N-methyl-D-aspartate receptor antagonists to enhance cognition and decelerate neurodegeneration CNS & neurological disorders drug targets · 2014-02-01 · usefulness score 34/100

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