Neural Regulation of Cerebral Blood Flow in Alzheimer's Disease and Under Normal Circumstances

This article [Iadecola, 2004: (http://www.ncbi.nlm.nih.gov/pubmed/15100718)] is interesting, and the author discusses the role that disturbances in neurovascular coupling may play in the development of Alzheimer's disease. The terminology that Iadecola (2004) uses is potentially confusing, and the message is essentially that cerebral blood flow (CBF) is likely to be regulated by neural inputs to glial cells and interneurons that are immediately adjacent to the smooth muscle cells of cerebral arteries and smaller arterioles. The concept that CBF is regulated directly or relatively directly by neural inputs to cerebral blood vessels is still controversial. It's more that there hasn't necessarily been broad acceptance of the concept that the neural regulation of CBF contributes meaningfully to autoregulation of CBF under normal circumstances or outside of specific sets of circumstances.

The interesting thing to me is the locations of the so-called "intrinsic neurons" that influence the neural regulation of regional CBF across many different parts of the brain. I'm not going to try to make any generalizations about disease processes, based on the sites of these "hubs" of neural CBF regulation. There's a lot of heterogeneity, even within the types of dementia, and it's really difficult to take information from anatomical pathways in the brain and draw conclusions about the processes underlying Alzheimer's disease. But it's interesting that three of the four sites listed are important sites of neuronal loss in Alzheimer's disease. The author discusses the blurring of the lines between Alzheimer's disease and vascular dementia but doesn't discuss these specific areas in any degree of detail. Those groups of neurons are involved in so many different processes that I suppose it's not appropriate to draw any conclusions based on their involvement in the neural regulation of CBF. But the three sites are, as listed in the article, the raphe, which usually refers to the serotonergic neurons of the dorsal raphe nuclei, the locus ceruleus, which is one of the main groups of noradrenergic neurons that express dopamine beta-hydroxylase (the enzyme that converts dopamine into noradrenaline), and the nucleus basalis [which is the nucleus basalis of Meynert (NBM), a.k.a. the nucleus of Meynert, in the basal forebrain].

The ventral tegmental area (VTA), the fourth site, contains a diverse range of neurons but contains, notably, dopaminergic neurons that project to the nucleus accumbens or prefrontal cortex. The VTA neurons that project to those sites are parts of the mesolimbic and mesocortical pathways, respectively. The authors of this article [Murray et al., 1995: (http://www.ncbi.nlm.nih.gov/pubmed/7695230)] found that the VTA is not a major site of neuronal loss in the brains of people with either Alzheimer's disease alone or Alzheimer's disease + Parkinsonism. Murray et al. (1995) did note that about a third of people with Alzheimer's disease have some degree of Parkinsonism, but advancing age per se increases the incidence of some symptoms of Parkinsonism. Loss of dopaminergic functioning is probably not very specific to Alzheimer's disease.

Iadecola (2004) also discussed the role of peroxynitrite in Alzheimer's disease.