Elsevier

Neurobiology of Aging

Volume 19, Issue 6, November–December 1998, Pages 505-510
Neurobiology of Aging

Original Articles
A sex difference and no effect of ApoE type on the amount of cytoskeletal alterations in the nucleus basalis of Meynert in Alzheimer’s disease

https://doi.org/10.1016/S0197-4580(98)00106-7Get rights and content

Abstract

In the nucleus basalis of Meynert (NBM) we studied the presence of early cytoskeletal alterations as shown by the antibody Alz-50 in ApoE-typed patients. Using an image analysis system, the area covered by Alz-50 staining and the percentage of neurons stained by Alz-50 were determined. There were no significant differences in the area covered by Alz-50 or in the proportion of Alz-50-stained neurons in the nucleus basalis of Meynert of Alzheimer’s disease (AD) patients with one or two ApoE ϵ4 alleles as compared with those without any ApoE e4 allele. However, there was a significant sex difference in Alz-50 staining: female Alzheimer’s disease patients showed more severe early cytoskeletal alterations than males. We also found a significant relationship between the number of Alz-50-stained neurons and the severity of dementia.

Section snippets

Tissue preparation

Brains of 36 AD patients ranging in age from 49 to 96 years were obtained at autopsy (see Table 1 for details and clinicopathological information). The patients were clinically assessed and diagnosed as “probable AD” by excluding other possible causes of dementia by history, physical examination and laboratory tests according to the diagnostic criteria as described by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders

Immunocytochemistry

In all AD patients immunocytochemical staining with Alz-50 revealed a very intense staining of NBM neuronal perikarya, neuropil threads and some dystrophic neurites (Fig. 1 ). Qualitative microscopic analysis showed that both the area occupied by Alz-50 staining (Alz-50 load) and the proportion of Alz-50-stained neurons in AD patients with the ApoE genotype ϵ3/3 showed much interindividual variation.

Alz-50 load or the total area covered by Alz-50 staining

A total of 5,264 images (each image 37,456 μm2) were analyzed. In order to determine the

Discussion

Earlier studies had shown that the NBM is not only heavily stained by Alz-50, but also by other antibodies showing cytoskeletal alterations. In AD, NBM neurons are, e.g., intensely stained by the 60e (against NFTs), tau-1 (against tau) and 3–39 (against ubiquitin) antibody. However, Alz-50 showed the most intense staining in the NBM of AD patients (48).

Alz-50 not only stains AD changes, but also cell bodies, e.g., in the periventricular nucleus of the hypothalamus of nondemented young controls

Acknowledgements

Brains were obtained from the Netherlands Brain Bank, Amsterdam, The Netherlands (coordinator Dr. R. Ravid). Alz-50 was kindly donated by Abbott Laboratories, Chicago, USA. We thank Dr. C. W. Pool for his essential help with the image analysis system and O. Pach for her secretarial assistance. Much appreciation to Dr. O. S. Jørgenson (Laboratory of Neuropsychiatry, University of Copenhagen, Denmark) for performing ApoE genotyping. The neuropathological diagnosis of Alzheimer’s disease was

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