Luteinizing hormone modulates cognition and amyloid-β deposition in Alzheimer APP transgenic mice

Gemma Casadesus, Kate M. Webber, Craig S. Atwood, Miguel Pappolla, George Perry, Richard L. Bowen, Mark A. Smith

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Until recently, the study of hormonal influences in Alzheimer disease was limited to the role of sex steroids. Despite numerous epidemiological studies supporting a protective role for estrogen in Alzheimer disease, recent studies show that estrogen administration in elderly women increases the risk of disease. Reconciling these contradictory reports, we previously hypothesized that other hormones of the hypothalamic-pituitary-gonadal axis, such as luteinizing hormone, may be involved in the onset and development of the disease. In this regard, luteinizing hormone is elevated in Alzheimer disease and is known to modulate amyloidogenic processing of amyloid-β protein precursor. Therefore, in this study, to evaluate the therapeutic potential of luteinizing hormone ablation, we administered a gonadotropin-releasing hormone analogue, leuprolide acetate, to an aged transgenic mouse model of Alzheimer disease (Tg 2576) and measured cognitive Y-maze performance and amyloid-β deposition after 3 months of treatment. Our data indicate that luteinizing hormone ablation significantly attenuated cognitive decline and decreased amyloid-β deposition as compared to placebo-treated animals. Importantly, leuprolide acetate-mediated reduction of amyloid-β correlated with improved cognition. Since both cognitive loss and amyloid-β deposition are features of Alzheimer disease, leuprolide acetate treatment may prove to be a useful therapeutic strategy for this disease.

Original languageEnglish (US)
Pages (from-to)447-452
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1762
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Luteinizing Hormone
Amyloid
Cognition
Transgenic Mice
Alzheimer Disease
Leuprolide
Estrogens
Hypothalamic Hormones
Pituitary Hormones
Amyloid beta-Protein Precursor
Therapeutics
Gonadotropin-Releasing Hormone
Epidemiologic Studies
Steroids
Placebos

Keywords

  • Alzheimer disease
  • Amyloid-β
  • Cognition
  • Hippocampal function
  • Luteinizing hormone
  • Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Luteinizing hormone modulates cognition and amyloid-β deposition in Alzheimer APP transgenic mice. / Casadesus, Gemma; Webber, Kate M.; Atwood, Craig S.; Pappolla, Miguel; Perry, George; Bowen, Richard L.; Smith, Mark A.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1762, No. 4, 04.2006, p. 447-452.

Research output: Contribution to journalArticle

Casadesus, Gemma ; Webber, Kate M. ; Atwood, Craig S. ; Pappolla, Miguel ; Perry, George ; Bowen, Richard L. ; Smith, Mark A. / Luteinizing hormone modulates cognition and amyloid-β deposition in Alzheimer APP transgenic mice. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2006 ; Vol. 1762, No. 4. pp. 447-452.
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