Changes in the Expression of Genes Associated with Intraneuronal Amyloid-β and Tau in Alzheimer's Disease

Issue title: Similarities and Differences Between Mild Cognitive Impairment and Alzheimer's Disease

Guest editors: Mark A. Lovell

Article type: Research Article

Authors: Fujimura, Robert K.^{a; *} | Reiner, Teresita^a | Ma, Fangchao^{a; 1} | Phillips, Virginia^b | de las Pozas, Alicia^a | Dickson, Dennis W.^b | Roos, Bernard A.^{a; c; d; e} | Howard, Guy A.^{a; c; f} | Perez-Stable, Carlos^{a; c; *}

Affiliations: [a] Geriatric Research, Education, and Clinical Center and Research Service, Bruce W. Carter Veterans Affairs Medical Center, Miami, FL, USA | [b] Department of Pathology, Mayo Clinic, Jacksonville, FL, USA | [c] Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA | [d] Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA | [e] Stein Gerontological Institute, Miami Jewish Home and Hospital, Miami, FL, USA | [f] Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA | Sanders-Brown Center on Aging and Alzheimer's Disease Center, Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA

Correspondence: [*] Corresponding authors: Robert K. Fujimura, Ph.D. and Carlos Perez-Stable, Ph.D., Bruce W. Carter VA Medical Center, GRECC (11-GRC), 1201 NW 16 Street, Miami, FL 33125, USA. Tel.: +1 305 575 3388; Fax: +1 305 575 3365; E-mail: [email protected].

Note: [1] Current Address: Department of Public Health, Division of Epidemiologic Studies, Illinois Department of Public Health, Springfield, IL, USA.

Abstract: The clinical hallmark of Alzheimer's disease (AD) is impairment of cognition associated with loss of synapses, accumulation of amyloid-β (Aβ) both within neurons and as extracellular deposits, and neurofibrillary degeneration composed of phospho-tau. Neurons in the hippocampus are among those that are most vulnerable. The purpose of this study was to investigate the expression of genes associated with cognition, synapse, and mitochondrial function in hippocampal neurons of AD compared to normal individuals. Neurons from the hippocampus with intraneuronal Aβ immunoreactivity were captured with laser microdissection; RNA was extracted; and levels of brain-derived neurotrophic factor (BDNF), TrkB (BDNF receptor), dynamin-1 (DYN), and cytochrome C oxidase subunit II (COX2) were assessed with quantitative real-time polymerase chain reaction. We found no significant differences in the expression of these genes in AD between neurons associated with Aβ compared to those lacking Aβ immunoreactivity. Double immunofluorescence microscopy showed the number of hippocampal neurons coexpressing Aβ or phospho-tau and either BDNF, TrkB, or DYN was similar in AD and controls. Our results suggest that neither intraneuronal Aβ nor phospho-tau has obligatory effects on reducing the expression of genes important for memory and cognition in hippocampus of AD.

Keywords: Amyloid-β, brain-derived neurotrophic factor (BDNF), cytochrome C oxidase subunit II (COX2), double immunofluorescence, dynamin-1 (DYN), qRT-PCR, phospho-tau

DOI: 10.3233/JAD-2010-1216

Journal: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 97-109, 2010