Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.
Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.
Yes
Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte
Good breeding capabilities and no premature death.
Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.
Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.