Fibrillary beta-amyloid deposits are closely associated with atrophic nitric oxide synthase (NOS)-expressing neurons but do not upregulate the inducible NOS in transgenic Tg2576 mouse brain with Alzheimer pathology

Transgenic mice (Tg2576) that express the Swedish double mutation of human amyloid precursor protein and develop Alzheimer-like beta -amyloid deposits in the aged brain, were used to study the effect of beta -amyloid depositi on on expression of both neuronal (nNOS) and inducible nitric oxide synthas e (iNOS) in cells surrounding beta -amyloid plaques. Nicotinamide adenine d i nucleotide phosphate-diaphorase histochemistry and double immunofluoresce nt labeling revealed that most of the fibrillary, thioflavine-S-positive co rtical beta -amyloid deposits in 13-, 17-, and 21-month-old transgenic anim als were closely associated with dystrophic nNOS-positive neurons, while nN OS-bearing neurons located more distal to plaques appeared to be unaffected . There was no significant expression of iNOS in transgenic mouse brain. Th e data suggest enhanced vulnerability of nNOS-containing neocortical neuron s to beta -amyloid toxicity. Alternatively, expression of nNOS may also be a response to plaque-mediated damage of neurons, consistent with a neuropro tective role of nitric oxide. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.