Alterations of the cerebral capillary bed in the senile dementia of Alzheimer
Tóm tắt
Brain tissue specimens from 15 patients dying with neuropathologically confirmed clinical diagnoses of senile dementia, Alzheimer type, and 10 approximately age and sex matched elderly patients without signs of senile change, were compared using a group of neurohistological techniques including scanning electron microscopy. In addition to previously described changes in structure of neurons and neuropil, dramatic changes were noted in the capillary bed. Normal cerebral vessels are characterized by smooth contours, the presence of occasional pericytes, and a plexus of pericapillary nerve fibers bearing many varicosities which have been shown to be strongly positive for norepinephrine, acetylcholine, dopamine and several other putative neurotransmitters or neuromodulators. In our series of Alzheimer patients the cerebral vessels were highly irregular in appearance, covered with rounded or conical extrusions (lumps and bumps), and totally lacking in the perivascular plexus of nerve fibers. In about three quarters of the cases studied the vessel walls were perforated by multiple openings of varying sizes, most of which appeared to run through the complete thickness of the thickened basement membrane but did not perforate the endothelial lining of the capillary lumen. The origin and pathogenesis of these changes is still unknown although some of the materials infiltrating the vascular walls appear to contain amyloid. On the basis of presently available evidence, it is suggested that widespread microvascular pathology may be caused by loss of the perivascular neural plexus (denervating microangiopathy) and that this may result in breakdown of the blood brain barrier. It is conceivable that the widespread degeneration characteristic of senile domentia, Alzheimer type, develops secondarily to these structuro-functional alterations in the microvasculature and that the primary target of the Alzheimer process may be located in subcortical nuclei, e.g. locus ceruleus and nucleus basalis of Meynert, which normally supply innervation to the cerebral vessels.
Tài liệu tham khảo
Bell M.A., Ball M.J.:Morphometric comparison of hippocampal microvasculature in aging and demented people: diameters and densities. Acta Neuropathol. 53: 299–318, 1981.
Bondareff W., Mountjoy C.O., Roth M.:Loss of neurons of origin of the adrenergic projection to cerebral cortex in senile dementia. Neurology 32: 164–168, 1982.
Brayden J.E., Bevan J.A.:Neurogenic muscarinic vasodilatation in the cat. Circ. Res. 56: 205–211, 1985.
Edvinssn L.:Functional role of perivascular peptides in the control of cerebral circulation. Trends in Neurosci. 8: 126–131, 1985.
Edvinson L., Lindvall M., Nielsen K.C., Owman C.H.:Are brain vessels innervated also by central (non-sympathetic) adrenergic neurons? Brain Res. 63: 469–499. 1973.
Glenner G.G.:Current knowledge of amyloid deposits as applied to senile plaques and congophilic angiopathy. Aging NY 7: 493–501, 1978.
Glenner G.G., Wong C.W.:Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120: 885–890, 1984.
Goldgaber D., Lerman M.I., McBride O.W., Saffretti U., Gajchusek D.C.:Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s Disease. Science 235: 877–880, 1987.
Gunn C.G.:Proliferative nature of arteriosclerosis and regulators of metabolism and movement. In: Wolfe, S. (Ed.). The Artery and the Process of Arteriosclerosis, New York, Plenum Press, 56 et seq.; 230 et seq. 1971.
Hartman B.K.:The innervation of cerebral blood vessels by central noradrenergic neurons. In: Usden, E., Snyder, S. (Eds.), Frontiers in Catecholamine Research. New York, Pergamon Press, 91–96, 1973.
Hassler O.:Vascular changes in senile brains. Acta Neuropathol. (Berlin) 1965; 5: 40–53.
Itakura T., Yamamoto K., Tohyama M., Shimizu N.:Central dual innervation of arterioles and capillaries in the brain. Stroke 8: 360–365.
Raichle M.E., Hartman B.K., Eichling J.O., Sharpe L.G.:Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc. Natl. Acad. Sci.; 72: 3726–3730, 1975.
Ravens J.R.:Vascular changes in the human senile brain. In: Cervós-Navarro, J., Betz, E., Eberhardt, G., Ferst, R., Wullenweber, XX (Eds.), Pathology of Cerebrospinal Microcirculation: Vol. 20, Advances in Neurology. New York, Raven Press, 487–501, 1978.
Rennels M.L., Nelson E.:Capillary innervation in the mammalian central nervous system. Am. J. Anat.; 144: 233–241, 1975.
Ccheibel A.B., Duong T., Tomiyasu, U.:Microvascular changes in Alzheimer’s Disease. In: A.B. Scheilbel and A. Websters (Eds.), The Biological Substrates of Alzheimer’s Disease. New York, Academic Press; 177–192, 1986.
Scheibel A.B., Fried I.:Age-related changes in the peri-capillary environment. In: Samuel D., Algeri, A., Gershon, S., Grimm, V.E., Toffano, G. (Eds.), Aging of the Brain: Vol. 22, The Aging Series, New York, Raven Press; 81–92, 1983.
Scheibel M.E., Lindsay R.D., Romiyasu U., Scheibel A.B.:Progressive dendritic changes in aging human cortex. Exp. Neurol. 47: 392–403, 1975.
Scremin O.U., Rovere A.A., Raynald A.C., Giardni A.:Cholinergic control of blood flow in the cerebral cortex of the cat, Stroke; 4: 232–239, 1974.
St. George-Hyslop P., Tanzi R.E., Polinsky R.J., Haines J.L., Nee L., Watkins D.C., Myers R.W., Feldman R.G., Pollen D., Drachman D., Gowdon, J., Buni A., Foncin J.F., Salmon D., Frommelt, P., Amaducci L., Sorbi S., Piacentini S., Stewart G.D., Hobbs W.J., Conneally P.M., Gusella J.F.:The genetic defect causing familial Alzheimer’s Disease maps on Chromosome 21. Science; 235: 885–590, 1987.
Terry R.D.:Ultrastructural studies in Alzheimer’s presenile dementia. Am. J. Pathol.; 44: 269–281. 1964.
Tuke J.B.:On the morbid histology of the brain and spinal cords as observed in the insane. Br. For. Med. Chir. Rev.; 51: 450–460, 1873.
Whitehouse P.J., Price D.L., Clark A.W., Coyle J.T., De Long M.R.:Alzheimer’s disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. An. Neurol. 10: 122–126, 1981.