The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease

Justin C. Shenk, Jiankang Liu, Kathryn Fischbach, Kui Xu, Michelle Puchowicz, Mark E. Obrenovich, Eldar Gasimov, Ludis Morales Alvarez, Bruce N. Ames, Joseph C. LaManna, Gjumrakch Aliev

Research output: Contribution to journalArticle

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Abstract

We measured age-dependent effects of human ApoE4 on cerebral blood flow (CBF) using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice by use of [ 14 C] iodoantipyrene autoradiography. ApoE4 associated factors reduce CBF gradually to create brain hypoperfusion when compared to WT, and the differences in CBF are greatest as animals age from 6-weeks to 12-months. Transmission electron microscopy with colloidal gold immunocytochemistry showed structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the cytoplasm of perivascular cells, perivascular nerve terminals and hippocampal neurons and glial cells. These abnormalities coexist with mitochondrial structural alteration and mitochondrial DNA overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed selective mitochondrial antioxidants acetyl-l-carnitine and R-α-lipoic acid. Our findings indicate that ApoE4 genotype-induced mitochondrial changes and associated structural damage may explain age-dependent pathology seen in AD, indicating potential for novel treatment strategies in the near future.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalJournal of the Neurological Sciences
Volume283
Issue number1-2
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

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Acetylcarnitine
Apolipoprotein E4
Thioctic Acid
Cerebrovascular Circulation
Alzheimer Disease
Therapeutics
Neurons
Gold Colloid
Brain
Microvessels
Autoradiography
Transmission Electron Microscopy
Mitochondrial DNA
Neuroglia
Cognition
Transgenic Mice
Endothelium
Cytoplasm
Antioxidants
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease. / Shenk, Justin C.; Liu, Jiankang; Fischbach, Kathryn; Xu, Kui; Puchowicz, Michelle; Obrenovich, Mark E.; Gasimov, Eldar; Alvarez, Ludis Morales; Ames, Bruce N.; LaManna, Joseph C.; Aliev, Gjumrakch.

In: Journal of the Neurological Sciences, Vol. 283, No. 1-2, 15.08.2009, p. 199-206.

Research output: Contribution to journalArticle

Shenk, JC, Liu, J, Fischbach, K, Xu, K, Puchowicz, M, Obrenovich, ME, Gasimov, E, Alvarez, LM, Ames, BN, LaManna, JC & Aliev, G 2009, 'The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease', Journal of the Neurological Sciences, vol. 283, no. 1-2, pp. 199-206. https://doi.org/10.1016/j.jns.2009.03.002
Shenk, Justin C. ; Liu, Jiankang ; Fischbach, Kathryn ; Xu, Kui ; Puchowicz, Michelle ; Obrenovich, Mark E. ; Gasimov, Eldar ; Alvarez, Ludis Morales ; Ames, Bruce N. ; LaManna, Joseph C. ; Aliev, Gjumrakch. / The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease. In: Journal of the Neurological Sciences. 2009 ; Vol. 283, No. 1-2. pp. 199-206.
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