Elsevier

Neuroscience

Volume 83, Issue 4, 12 January 1998, Pages 991-1002
Neuroscience

Cortical distribution of neurofibrillary tangles in Alzheimer's disease matches the pattern of neurons that retain their capacity of plastic remodelling in the adult brain

https://doi.org/10.1016/S0306-4522(97)00509-5Get rights and content

Abstract

The formation of neurofibrillary tangles in Alzheimer's disease shows a preferential involvement of certain cytoarchitecturally defined cortical areas suggesting systematic differences in regional neuronal vulnerability. The cellular and molecular nature of this selective neuronal vulnerability that follows a certain hierarchy of structural brain organization is largely unknown. In the present study, we compared the regional pattern of tangle density in Alzheimer's disease with systematic regional differences in neuronal plasticity that can be observed both during ageing and in Alzheimer's disease. Changes in dendritic length and arborization of Golgi-impregnated pyramidal neurons were analysed after three-dimensional reconstruction in 12 cortical areas. The intensity of dendritic remodelling that was observed during ageing as well as in Alzheimer's disease was regionally different and decreased in the following order: transentorhinal region >limbic areas (entorhinal region, hippocampus)>non-primary association areas (37, 40, 46)>primary sensory association areas (7, 18, 22)>primary sensory and motor cortex (17, 41, 4). These regional differences of neuronal plasticity follow the same pattern as the regional vulnerability to tangle formation in Alzheimer's disease.

The results of the present study provide evidence that a high degree of structural neuronal plasticity might predispose neurons to tangle formation.

Section snippets

Cases

Brains were obtained from 64 patients with AD and from 61 control patients. The profile of cases is summarized in Table 1. The clinical diagnosis of AD was based on the occurrence of significant intellectual dysfunction, i.e. the presence of deficits in at least four aspects of cognitive and social behaviour. Other causes of dementia were excluded by medical, psychiatric and paraclinical examination (Diagnostic and Statistical Manual of Mental Disorders, DSM-IIIR, American Psychiatric

Dendritic remodelling of pyramidal neurons

To obtain a measure of structural neuronal plasticity in the adult brain, changes in total length of apical and basal dendrites of pyramidal neurons and their degree of ramification was analysed in 12 cortical areas. Data are summarized in Fig. 1, Fig. 2, Table 2, averaged for the following five groups: (i) adult controls, (ii) senior controls, (iii) elderly controls, (iv) AD cases without ApoE epsilon 4 allele and (v) AD cases carrying one or two ApoE epsilon 4 alleles. Fig. 3 illustrates the

Regional differences in neuronal plasticity

The results of the present study demonstrate a regionally different structural plasticity in the cerebral cortex of the human brain during ageing. These observations are in agreement with a variety of previous studies on rodent, monkey and human brain that have been reported on marked regional differences in neuronal plasticity in the ageing brain as measured by the dendritic extent (for review see [28]).

A continued age-related net dendritic growth has been described in layer II pyramidal

Conclusion

It is tempting to speculate that general differences in the dynamics of structural organization of both subcortical and cortical areas might be related to the function which this brain areas subserves. Against the background of this hypothesis, it can be predicted that primary sensory and motor areas should display a higher degree of structural stability than limbic, paralimbic and associative areas that are involved in the processing and storage of information. It appears that some principles

Acknowledgements

This study was supported by the Bundesministerium für Bildung, Forschung und Technologie (BMBF), Interdisciplinary Centre for Clinical Research at the University of Leipzig (01KS9504, Project C1).

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