Intracellular Aβ and cognitive deficits precede β-amyloid deposition in transgenic arcAβ mice

The brain pathology of Alzheimer’s disease is characterized by abnormally aggregated A in extracellular -amyloid plaques and along blood vessel walls, but the relation to intracellular A remains unclear. To address the role of intracellular A deposition in vivo ,w e expressed human APP with the combined Swedish and Arctic mutations in mice (arcA mice). Intracellular punctate deposits of A occurred concomitantly with robust cognitive impairments at the age of 6 months before the onset of -amyloid plaque formation and cerebral amyloid angiopathy. -Amyloid plaques from arcA mice had distinct dense-core morphologies with blood vessels appearing as seeding origins, suggesting reduced clearance of A across blood vessels in arcA mice. The co-incidence of intracellular A deposits with behavioral deficits support an early role of intracellular A in the pathophysiological cascade leading to -amyloid formation and functional impairment.

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