• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• spatial working memory defects observed in Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice are rescued (J:169481)

• mice exhibit improved motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice (J:169481)

• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• mice exhibit decreased alternation frequency in a Y maze compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• mice exhibit impaired motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

• impaired survival compared to wild-type mice and transgenic mice wild-type for Apoa4

• large pyramidal neurons in cortical layer 5 and neurons in hippocampus contain more disrupted morphologies indicating enhanced neuron loss compared to transgenic mice wild-type for Apoa4

• loss of neurons is increased in areas of the cortex and CA1, CA3 of the hippocampus

• accelerated deposition compared to transgenic mice wild-type for Apoa4

• impaired spatial learning (slower decrease in escape latency during training in a morris water maze) compared to transgenic mice wild-type for Apoa4

• more time spent in the incorrect quadrant in a probe trial in a morris water maze compared to transgenic mice wild-type for Apoa4

• accelerated deposition compared to transgenic mice wild-type for Apoa4

• by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory

• transgenic mice display neuroinflammation

• cortical layer 1 is significantly thinner than in control brains

• neurons in subiculum are very pale, or absent

• microgliosis and astrogliosis is seen in plaque-bearing regions of the brain by 2 months of age; numbers of activated astrocytes and microglia increases with age

• some neurons contain intraneuronal aggregates and display disrupted morphology

• large neurons in cortical layer 5 are reduced in number

• mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

• amyloid deposition increases rapidly with increasing age

• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

• synapse degeneration begins at 4 months of age, compared to nontransgenic controls, as shown by reduction in levels of synaptic markers; neurodeneration marker p25 level is ~150% of control at 9 and 12 months

• transgenic mice display neuroinflammation

• mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

• amyloid deposition increases rapidly with increasing age

• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

• impaired survival compared to wild-type mice

• survive longer than transgenic mice that are also Apoa4 null