• in 1-year old animals, a relatively high number of cholinergic fiber aggregates in the cortex are observed in transgenic; at 20 months of age, a few such areas of densed cholinergic fiber aggregations are observed in other APP-targeted mice

• cholinergic fibers of large diameter are seen in layer 1 of the entorhinal cortex in mutant transgenic mice more prominently than in the other strains, but such fibers are present even in controls

• clusters of ballooned and spherical acetylcholine-immunoreactive terminals are observed in the periphery of compact amyloid plaques around the amyloid core in 12-month old animals, and numbers increase with age and plaque load

• amyloid plaques are detected in the brains of these mutant transgenic mice but not in App transgenic or App Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age

• amyloid plaques are detected in the brains of these mutant transgenic mice but not in App transgenic or App Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age

• ins some areas of cortex in older animals,astrocytes appear dystrophic and are no longer closely associated with plaques, although nearby plaques are associated with activated glial cells

• activated astrocytes accumulate around amyloid deposits in frontal cortex of 3 month old mice

• activated microglia accumulate around amyloid beta deposits from ~ 3 months; number of glia increases with age and amyloid accumulation

• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus

• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age

• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age

• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age

• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus

• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age

• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age

• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age

• microgliosis and astrocytosis reduced in the hippocampus, and entorhinal cortex

• astrocytosis also reduced in the cingulated cortex

• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques

• equal levels of alpha- and beta-CTF

• antibody to CD40L produces increased levels of circulating beta amyloid

• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques

• equal levels of alpha- and beta-CTF

• antibody to CD40L produces increased levels of circulating beta amyloid

• some mutants older than 18 months exhibit amyloid deposits in the spleen and kidneys, and occasionally in the liver, ovary and/or heart

• amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen

• in the liver, amyloid deposit is in the walls of sinusoids or central veins

• in the kidney, amyloid deposits are seen in the glomeruli

• amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A

• kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla