title: Impaired performance of female APP/PS1 mice in the Morris water maze is coupled with increased Aβ accumulation and microglial activation.
abstract: BACKGROUND
  Alzheimer's disease (AD) is characterized by progressive neuronal loss and cognitive decline. Epidemiological studies suggest that the risk of AD is higher in women even when data are adjusted for age.
  
  
  OBJECTIVE
  We set out to compare changes in 9-month-old male and female mice which overexpress amyloid precursor protein (APP) with presenilin (PS1; APP/PS1 mice) and to evaluate whether any changes were coupled with deficits in spatial learning.
  
  
  METHODS
  APP/PS1 mice were assessed for their ability to learn in the Morris water maze and Aβ burden assessed by Congo Red and Aβ triple ultrasensitive assay. Neuroinflammatory changes were examined in brain tissue along with expression of Aβ-generating and Aβ-degrading enzymes.
  
  
  RESULTS
  A deficit in reversal phase learning in the Morris water maze was observed in female mice and was paralleled by evidence of increased accumulation of Aβ, microglial activation and expression of IL-1β. Accumulation of Aβ was coupled with an increase in expression of BACE-1 and a decrease in insulin-degrading enzyme (IDE).
  
  
  CONCLUSIONS
  The results indicate that the observed impairment in spatial memory in female APP/PS1 mice correlated with increased Aβ burden and the changes in Aβ may have occurred as a result of enhanced BACE-1 and decreased IDE expression.
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gallagher
authors.forename: A M
authors.initials: AM
authors.lastname: Minogue
authors.forename: M A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007339:Insulysin / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D012727:Sex Characteristics; D000097382:CD68 Molecule
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016282:Aspartic Acid Endopeptidases; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D007339:Insulysin; D053583:Interleukin-1beta; D015260:Neprilysin; D053764:Presenilin-1; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508853:PSEN1 protein, human; C509282:Bace1 protein, mouse