homeostasis/metabolism phenotype

• amyloid beta deposits
  • intraneuronal oligomers are detected at 4-6 months of age
  (MGI Ref ID J:107286)
  • Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
  (MGI Ref ID J:107286)

nervous system phenotype

• neurofibrillary tangles
  • tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months
  (MGI Ref ID J:107286)

• amyloid beta deposits
  • Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
  (MGI Ref ID J:107286)
  • intraneuronal oligomers are detected at 4-6 months of age
  (MGI Ref ID J:107286)

nervous system phenotype

• amyloid beta deposits
  • Normal - treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala
  (MGI Ref ID J:99604)
  • at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
  (MGI Ref ID J:99604)
  • prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
  (MGI Ref ID J:99604)

behavior/neurological phenotype

• abnormal learning/memory/conditioning
  • short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours
  (MGI Ref ID J:99604)
  • in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice
  (MGI Ref ID J:99604)
  • at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention
  (MGI Ref ID J:99604)
  • Normal - after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired
  (MGI Ref ID J:99604)

• abnormal contextual conditioning behavior
  • at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours
  (MGI Ref ID J:99604)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • Normal - treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala
  (MGI Ref ID J:99604)
  • prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
  (MGI Ref ID J:99604)
  • at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
  (MGI Ref ID J:99604)

behavior/neurological phenotype

• abnormal behavior
  • mutants attend less accurately to short, spatially unpredictable stimuli when the attentional demand of the task is high and also show a general tendency to make more perseverative responses than wild-type mice
  (MGI Ref ID J:170670)
  • mutants initially respond as accurately as wild-type mice, however subsequently they fail to sustain their attention over the duration of the task, indicating reduced vigilance, or ability to sustain attention over a long period of time
  (MGI Ref ID J:170670)
  • treatment of mice with the cholinesterase inhibitor donepezil results in an enhanced ability to sustain attention
  (MGI Ref ID J:170670)