Cerebral cortex in Alzheimer’s disease

Neuritic (senile) plaques Microscopic lesions composed of fragmented axon terminals and dendrites surrounding a core of amyloid seen in the cerebral cortex in Alzheimer s disease. 

H, Giacobini E, de Vos RA, Steur EN, Maelicke A, Albuquerque EX, Schroder H (1999) Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer s disease histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein. Eur J Neurosci 11 2551-2565... 

Albasanz JL, Dalfo E, Ferrer I et al (2005) Impaired metabotropic glutamate receptor/ phospholipase C signaling pathway in the cerebral cortex in Alzheimer s disease and dementia with Lewy bodies correlates with stage of Alzheimer s-disease-related changes. Neurobiol Dis 20 685-693... 

Kalaria, R.N. and Harik, S.I. (1989) Reduced glucose transporter at the blood brain barrier and in cerebral cortex in Alzheimer s disease. J. Neurochem. 53 1083-1088. 

Reductions in corticotropin releasing factor-like immunoreactivity in cerebral cortex in Alzheimer s disease, Parkinson s disease, and progressive supranuclear palsy. Neurology 37 905-909. 

Mullaart, E., Boerrigter, M.E., Ravid, R., Swaab, D.R and Vijg, J. 1990. Increased levels of DNA breaks in cerebral cortex of Alzheimer s disease patients. Neurobiol. Aging 11 169-173... 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

Cortical and hippocampal pyramidal cells are noteworthy in at least three ways (1) they are preferentially, but not exclusively, innervated by cholinergic terminals (2) they are implicated as a potential site of consciousness and (3) they are enriched with cytoskeletal proteins, some of which undergo hyperphosphorylation in Alzheimer s disease. A novel signal transduction mode may exist within the large pyramidal cells of the cerebral cortex and hippocampus. 

Mesulam, M.M. (1996) The systems-level organization of cholinergic innervation in the human cerebral cortex and its alterations in Alzheimer s disease. Prog Brain Res 109 285-297. 

Whitehouse PJ, Price DL, Clark AW, et al Alzheimer disease evidence for selective loss of cholinergic neurons in the nucleus basahs. Ann Neurol 10 122-126, 1981 Whitehouse PJ, Price DL, Struble RG, et al Alzheimer s disease and senile dementia—loss of neurons in the basal forebrain. Science 215 1237-1239, 1982 Whitehouse PJ, Hedreen JC, White CL, et al Basal forebrain neurons in dementia of Parkinson s disease. Ann Neurol 13 243-248, 1983 Whitehouse P, Martino A, Antuono P, et al Nicotinic acetylcholine binding sites in Alzheimer s disease. Brain Res 371 146-151, 1986 Whitehouse PJ, Martino AM, Marcus KA, et al Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch Neurol 45 722-724, 1988 Whitton PS, Sama GS, O Connell MT The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal diasylates in vivo. Neuropharmacology 39 1-4, 1991 Whitworth P, Kendall DA Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices. J Neurochem 51 258-265, 1988... 

Gabriel SM, Biere LM, Haroutunian V et al (1993) Widespread deficits in somatostatin but not neuropeptide Y concentrations in Alzheimer s disease cerebral cortex. Neurosci Lett 155 116-20 Gage PW (1992) Activation and modulation of neuronal K+ channels by GABA. Trends Neurosci 15 46-51... 

Gibson, A. M., Edwardson, J. A., McDermott, J. R. Post mortem levels of some brain peptidases in Alzheimer s disease reduction in proline endopeptidase activity in cerebral cortex. Neurosci. Res. Commun. 1991,9 73-81. 

Haug, L.S., Ostvold, A.C., Cowburn, R.F., Garlind, A., Winblad, B., Bogdanovich, N., and Walaas, S.I., 1996, Decreased inositol (l,4,5)-trisphosphate receptor levels in Alzheimer s disease cerebral cortex Selectivity of changes and possible correlation to pathological severity. 

Cholinergic neurons of the brain are of two types. There are interneurons which are intrinsic to the striatum of the basal ganglia (that is entirely confined to a group of neurons of the forebrain), and projecting neurons which have their cell bodies in one part of the brain but then have axons that deliver their output in a different part.51 There are a number of different pathways of projecting neurons some of which are known to be crucial in important diseases. For example, the neurons of the nucleus basalis of Maynert project extensively in the cerebral cortex, and it is these neurons which are known to degenerate in Alzheimer s disease. 

The Mi receptors sometimes are termed neural" because of their abundance in the cerebral cortex, hippocampus, and striatum. The Mi receptors have been implicated in Alzheimer s disease and are thought to be involved with such functions as memory and learning. Early studies suggested that the agonist McN-A-343 was selective for the Mi receptor, but more recent evidence indicates otherwise. It may show moderate selectivity for ... 

Li, Z., Okamoto, K., Hayashi, Y. and Sheng, M. 2004b. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119 873-887 Li, G., Yin, H. and Kuret, J. 2004c. Casein kinase 16 phosphorylates tau and disrupts its binding to microtubules. J. Biol. Chem. 279 15938-15945 Lian, Q., Ladner, C.J., Magnuson, D. and Lee, J.M. 2001. Selective changes of calcineurin (protein phosphatase 2B) activity in Alzheimer s disease cerebral cortex. Exp. Neurol. 167 158-165... 

The older hypothesis in which aluminium was said to be involved in the progress of Alzheimer s disease has generated much controversy [37]. It nevertheless inspired the development of early models for Alzheimer s disease. Intracerebral administration of aluminium in rabbits brings about neurofibrillary degeneration in several brain regions and a decrease of choline acetyl transferase in the striatum, but not in the cerebral cortex and hippocampus where the decrease mostly occurs in Alzheimer s disease [38], no amyloid plaques are formed and few changes in other neurotransmitter systems and behaviour have been reported [39]. 

Finally, it should be noted that not only are KSPGs present in the normal brain, associated with most neurons of the cerebral cortex, for example, but also that the epitope for highly sulfated KS chains disappears from these neurons in Alzheimer s disease [55]. However, the periphery of Alzheimer s disease neuritic plaques is positive for KS [56]. 

Figure 18.1 Typical tangle (T) and plaque (P) as visualised by silver impregnation in the cerebral cortex of a case of Alzheimer s disease. The extracellular plaque (10-50 pm diameter) consists of a central core of amyloid surrounded by glial processes and a number of neurites in a ring formation. The intracellular cytoplasmic tangle is composed of helical filaments in a paired format. (Reproduced with permission of Academic Press from Wischik and Crowther 1986)...

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