Transgenic mice overexpressing Swedish mutant human amyloid precursor prote
in and mutant presenilin-1 transgenes produce brain extracellular immuno-de
posits of beta-amyloid protein (A beta), closely associated with hyperphosp
horylated tau, Similar extracellular A beta deposits were also found in bra
in sections from cortex and hippocampus of Alzheimer's disease (AD) patient
s. In contrast to the mouse brain, however, hyperphosphorylated tau in the
AD brain was found in distinct intracellular neurofibrillary tangles, rathe
r than being associated with A beta. Also associated with the A beta/tau de
posits in the double transgenic mice was immunostaining for JNK1, a stress-
activated protein kinase, present in both phosphorylated (active) and non-p
hosphorylated (inactive) forms. No corresponding staining was observed in t
he AD brain. Some evidence for expression of stress-activated protein kinas
e 3 (SAPK3) was also noted uniquely in the transgenic mouse brain, although
this was not so obviously associated with the A beta/tau. These results su
ggest that in this transgenic mouse line, A beta and hyperphosphorylated ta
u production are linked by a process that may involve stress-activated prot
ein kinases.