Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type.

Alzheimer's disease (AD) is the most common form of dementia, with progressive cognitive deficits being the primary symptom. AD is neuropathologically characterized by amyloid and neurofibrillary tangle depositions, basal forebrain cholinergic deficit, and extensive neuronal loss and synaptic changes in the cortex and hippocampus. Mutations of amyloid precursor protein or presenilin genes or apolipoprotein E gene polymorphism appear to affect amyloid formation, which in turn causes neuronal death via a number of possible mechanisms, including Ca(2+) homeostasis disruption, oxidative stress, excitotoxicity, energy depletion, neuro-inflammation and apoptosis. Nitric oxide (NO) is an enzymatic product of nitric oxide synthase, which exists in three isoforms. In addition to its vasoactive and immunological properties, NO has significant neurophysiological functions. However, NO can also be neurotoxic primarily due to its free radical properties, and it has been implicated in neurodegenerative diseases. Interestingly, there is increasing evidence that NO may have a role in the aforementioned AD pathogenetic mechanisms, and putative links between NO and AD are beginning to be recognized. This review focuses on these issues highlighting the possible relevance of NO in AD, either as a neuroprotective or neurotoxic agent.