Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects

Jennifer C. Naylor, Jason D. Kilts, Christine M. Hulette, David C. Steffens, Dan G. Blazer, John F. Ervin, Jennifer L. Strauss, Trina B. Allen, Mark W. Massing, Victoria M. Payne, Nagy Adel Youssef, Lawrence J. Shampine, Christine E. Marx

Research output: Contribution to journalArticle

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Abstract

The neurosteroid allopregnanolone has pronounced neuroprotective actions, increases myelination, and enhances neurogenesis. Evidence suggests that allopregnanolone dysregulation may play a role in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. Our prior data demonstrate that allopregnanolone is reduced in prefrontal cortex in male patients with AD compared to male cognitively intact control subjects, and inversely correlated with neuropathological disease stage (Braak and Braak). We therefore determined if allopregnanolone levels are also reduced in AD patients compared to control subjects in temporal cortex, utilizing a larger set of samples from both male and female patients. In addition, we investigated if neurosteroids are altered in subjects who are APOE4 allele carriers. Allopregnanolone, dehydroepiandrosterone (DHEA), and pregnenolone levels were determined in temporal cortex postmortem samples by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography (40 subjects with AD/41 cognitively intact control subjects). Allopregnanolone levels are reduced in temporal cortex in patients with AD (median 2.68 ng/g, n = 40) compared to control subjects (median 5.64 ng/g, n = 41), Mann-Whitney p = 0.0002, and inversely correlated with Braak and Braak neuropathological disease stage (Spearman r = - 0.38, p = 0.0004). DHEA and pregnenolone are increased in patients with AD compared to control subjects. Patients carrying an APOE4 allele demonstrate reduced allopregnanolone levels in temporal cortex (Mann-Whitney p = 0.04). In summary, our findings indicate that neurosteroids are altered in temporal cortex in patients with AD and related to neuropathological disease stage. In addition, the APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD.

Original languageEnglish (US)
Pages (from-to)951-959
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1801
Issue number8
DOIs
StatePublished - Aug 1 2010

Fingerprint

Pregnanolone
Temporal Lobe
Alzheimer Disease
Neurotransmitter Agents
Pregnenolone
Dehydroepiandrosterone
Alleles
Neurobiology
Neurogenesis
Prefrontal Cortex
Neurodegenerative Diseases
Gas Chromatography-Mass Spectrometry
High Pressure Liquid Chromatography

Keywords

  • Alzheimer's disease
  • DHEA
  • allopregnanolone
  • neurosteroid
  • postmortem
  • pregnenolone
  • temporal cortex

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects. / Naylor, Jennifer C.; Kilts, Jason D.; Hulette, Christine M.; Steffens, David C.; Blazer, Dan G.; Ervin, John F.; Strauss, Jennifer L.; Allen, Trina B.; Massing, Mark W.; Payne, Victoria M.; Youssef, Nagy Adel; Shampine, Lawrence J.; Marx, Christine E.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1801, No. 8, 01.08.2010, p. 951-959.

Research output: Contribution to journalArticle

Naylor, JC, Kilts, JD, Hulette, CM, Steffens, DC, Blazer, DG, Ervin, JF, Strauss, JL, Allen, TB, Massing, MW, Payne, VM, Youssef, NA, Shampine, LJ & Marx, CE 2010, 'Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects', Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, vol. 1801, no. 8, pp. 951-959. https://doi.org/10.1016/j.bbalip.2010.05.006
Naylor, Jennifer C. ; Kilts, Jason D. ; Hulette, Christine M. ; Steffens, David C. ; Blazer, Dan G. ; Ervin, John F. ; Strauss, Jennifer L. ; Allen, Trina B. ; Massing, Mark W. ; Payne, Victoria M. ; Youssef, Nagy Adel ; Shampine, Lawrence J. ; Marx, Christine E. / Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2010 ; Vol. 1801, No. 8. pp. 951-959.
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