Changes in the expression of genes associated with intraneuronal amyloid-beta and tau in Alzheimer's disease.
The clinical hallmark of Alzheimer's disease (AD) is impairment of cognition associated with loss of synapses, accumulation of amyloid-beta (Abeta) 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 Abeta 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 Abeta compared to those lacking Abeta immunoreactivity. Double immunofluorescence microscopy showed the number of hippocampal neurons coexpressing Abeta or phospho-tau and either BDNF, TrkB, or DYN was similar in AD and controls. Our results suggest that neither intraneuronal Abeta nor phospho-tau has obligatory effects on reducing the expression of genes important for memory and cognition in hippocampus of AD.
Fujimura
Robert K
RK
Geriatric Research, Education, and Clinical Center and Research Service, Bruce W. Carter Veterans Affairs Medical Center, Miami, FL 33125, USA. kanjirob@yahoo.com
Reiner
Teresita
T
Ma
Fangchao
F
Phillips
Virginia
V
de las Pozas
Alicia
A
Dickson
Dennis W
DW
Roos
Bernard A
BA
Howard
Guy A
GA
Perez-Stable
Carlos
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D008137:Longitudinal Studies; D024101:Mitochondrial Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D013569:Synapses / Q000235:genetics; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
D016229:Amyloid beta-Peptides; D024101:Mitochondrial Proteins; D016875:tau Proteins