A Modular Arrangement of Neuronal Processes in Human Cortex: Disruption With Aging and in Alzheimer's Disease

Abstract

Studies were undertaken to assess whether or not neuron-specific immunostaining of the human brain can reveal unique cytoarchitectural features that may be affected by healthy aging and Alzheimer's disease (AD). Human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were stained with an antibody raised against the neurofilament protein 200,000 molecular weight subunit (NFP-200) using an avidin-biotin immunolocalization procedure. Immunostaining of cortex was neuron-specific and highlighted axons in particular. This staining has revealed an orderly arrangement of horizontal and vertical axon bundles which form latticelike compartments or modules throughout most of the matrix of the two cortical areas studied. The ACC shows this pattern to be intact in individuals through the ninth decade, while the PFC there was blurring of the modularity beyond the fifth decade. Irrespective of the age-related blurring of the latticelike arrangement of axons in PFC, neurologically normal elderly individuals nevertheless showed a highly organized appearance to the cortical matrix. By contrast, patients with AD showed a marked disruption of the modular arrangement of fibers in PFC, but not ACC. Differences between PFC fibers in controls and AD patients were also demonstrated with an axon-specific monoclonal antibody that reacted with phosphorylated epitopes of the NFP-200. The chaotic appearance of fiber staining in PFC seen in patients with AD was noted to be present in one subject who died in an early stage of the disease. The possible significance of this previously unknown aspect of cortical cytoarchitecture for normal cognitive functioning in humans is discussed. (J Geriatr Psychiatry Neurol 1988;1:3-10).

Get full access to this article

View all access options for this article.

References

Cajal L. , Ramon S. : Histologie Du Systeme Nerveux de L'Homme et des Vertebres , Vol. 1, 2. Paris, Maloine, 1911.

Baillarger J. : Recherche sur le structure de la couche corticale des circonfulutions du cerveau. Mem Acad R Belg 1840;8: 149-183.

Meynert T. : Der bau der grosshirnrinde und seine ortichen verschiedenhaeiten, nebst einem pathologisch-anatomischem corollarium. Vierteljahresschr Psychiat 1867;1:77-93.

Remak R. : Anatomische beobachtungen uber das gehirm, das rucklenmark und die nervenwurzeln . Mullers Arch Anat Physiol Wiss 1841;506-522.

Mann Dma : The neuropathology of Alzheimer's disease: A review with pathogenetic, aetiological and therapeutic considerations. Mech Ageing Dev 1985;31:213-255.

Tomlinson BE , Blessed G. , Roth M. : Observations on the brains of demented old people. J Neurol Sci 1970;11:205-242.

Mann Dma , Yates PO , Marcgnicik B. : Some morphometric observations on the cerebral cortex and in hippocampus in Alzheimer's presenile dementia, senile dementia of Alzheimer type, and Down's syndrome in middle age. J Neurol Sci 1985;69:139-159.

Mountjoy CQ , Roth M. , Evans Njr , Evans HM : Cortical neuronal counts in normal elderly controls and demented patients . Neurobiol Aging 1983;4:1-11.

Terry RD , Peck A. , DeTeresa R. , et al: Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 1981;10:184-192.

10.

Whitehouse P. , Price DL , Struble RG , et al: Alzheimer's disease and senile dementia. Loss of neurones in the basal forebrain. Science 1982;215:1237-1239.

11.

Brown BA , Majocha RE , Staton DM , Marotta CA : Axonal polypeptides cross-reactive with antibodies to neurofilament proteins . J Neurochem 1983;40:299-308.

12.

Majocha RE , Marotta CA , Benes FM : Immunostaining of neurofilament protein in human postmortem cortex. A sensitive and specific approach to the pattern analysis of human cortical cytoarchitecture . Can J Biochem 1985;63:577-584.

13.

Marotta CA : Neurofilaments. Minneapolis, University of Minnesota Press, 1983.

14.

Marotta CA : Neuronal intermediate filaments, in Lajtha A (ed): Handbook of Neurochemistry, Vol 60. New York, Plenum Press, 1984, pp 281-314.

15.

Brun A. , Englund E. : Regional pattern of degradation in Alzheimer's disease: Neuronal loss and histopathological grading. Histopathology 1981;5:549-564.

16.

Sternberger LA , Sternberger NH : Monoclonal antibodies distinguish phosphorylated and non-phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 1983;80: 6126-6130.

17.

Blessed G. , Tomlinson BE , Roth M. : The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968;114:797-8111.

18.

Von Economo CF : The Cytoarchitectonics of the Human Cerebral Cortex. London, Oxford Medical Publications, 1919.

19.

Lorente de No R: The structure of the cerebral cortex, in Ful JF (ed): Physiology of the Nervous System. New York, Oxford University Press, 1938, pp 291-339.

20.

Woolsey TA , Van der Loos H. : The structural organization of layer IV in the somatosensory region (S1) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectural units. Brain Res 1970;17:205-242.

21.

Hubel DH , Wiesel TN : Sequence, regularity and geometry of orientation columns in the monkey striate cortex. J Comp Neurol 1974;158:267-294.

22.

Sousa-Pinta A. : The structure of the first auditory cortex (A1) in the cat. I. Light microscopic observations on its organization. Arch Ital Biol 1973;111:112-137.

23.

Woolsey CN : Organization of cortical auditory systems, in Rasmussen GL , Windle WF (eds): Neural Mechanisms of the Auditory and Vestibular Systems. Springfield, III, Thomas Publishing, 1960.

24.

Asanuma H. , Rosen I. : Functional role of afferent input to the monkey motor cortex. Brain Res 1972;40:3-5.

25.

Mountcastle VB : An organizing principle for cerebral function: The unit module and the distributed system, in Schmidtt FO , Worden FG (eds): The Neurosciences Fourth Study Program. Cambridge, Mass , MIT Press, 1979, pp 21-42.

26.

Whitehouse PJ , Price DL , Clark A. , et al: Alzheimer's disease and Down's syndrome . Ann NY Acad Sci 1981;396:145-164.

27.

Hyman BT , Van Hoesen GW , Kromer BA , Damasio AR : Perforant pathway changes and the memory impairment of Alzheimer's disease . Ann Neurol 1986;20:472-481.

28.

Scheibel AB , Tomiyasu U. : Dendritic sprouting in Alzheimer's presenile dementia. Exp Neurol 1978;60:1-8.