Elsevier

Neurobiology of Aging

Volume 18, Issue 4, July–August 1997, Pages 351-357
Neurobiology of Aging

Open Peer Commentaries
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories

https://doi.org/10.1016/S0197-4580(97)00056-0Get rights and content

Abstract

Alzheimer’s disease is a relentlessly progressing dementing disorder. Major pathological hallmarks include extracellular deposits of amyloid protein and intraneuronal neurofibrillary changes. No remissions occur in the course of the disease. Initial amyloid deposits develop in poorly myelinated areas of the basal neocortex. From there, they spread into adjoining areas and the hippocampus. Deposits eventually infiltrate all cortical areas, including densely myelinated primary fields of the neocortex (stages A–C). Intraneuronal lesions develop initially in the transentorhinal region, then spread in a predictable manner across other areas (stages I–VI). At stages I–II, neurofibrillary changes develop preferentially in the absence of amyloid deposits. A proportion of cases shows early development of amyloid deposits and/or intraneuronal changes. Advanced age is thus not a prerequisite for the evolution of the lesions. Alzheimer’s disease is an age-related, not an age-dependent disease. The degree of brain destruction at stages III–IV frequently leads to the appearance of initial clinical symptoms. The stages V–VI representing fully developed Alzheimer’s disease are increasingly prevalent with increasing age. The arithmetic means of the stages of both the amyloid-depositing and the neurofibrillary pathology increase with age. Age is a risk factor for Alzheimer’s disease.

Section snippets

Materials and Methods

A total of 2,661 brains obtained at autopsy was examined in this study. The brains were collected between 1986 and 1996 and were sent by three Departments of Pathology and one Department of Forensic Pathology belonging to three Universities in Germany. The material included cases from all the affiliated University clinics. It did not originate in special gerontopsychiatric institutions and does not correspond to such preselected material as might have been provided by a Department of

Results

The proportion of cases exhibiting no amyloid deposits or neurofibrillary changes decreases with advancing age (Fig. 2, Fig. 3, upper row). Neither amyloid deposits nor neurofibrillary changes necessarily accompany old age. The evolution of amyloid deposits is shown in Fig. 2 and Table 2. The subpopulations devoid of neurofibrillary changes are represented by the blank areas in the columns in Fig. 2, and the dark areas indicate the subgroups expressing any degree of neurofibrillary changes.

Discussion

The clinical diagnosis of AD is fraught with difficulty and definite diagnoses cannot presently be made. Both false positive and false negative diagnoses occur in a significant proportion of cases, underlining the necessity for postmortem evaluation. Epidemiological studies often focus on avoiding selection bias, yet still face the problem of inaccurate diagnoses 1, 17, 20, 22, 25, 27. Postmortem assessments offer the advantage of unambiguous diagnoses, however, they unavoidably fail to be

Acknowledgements

This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, and Degussa, Hanau. The skillful assistance of Ms. Szasz (drawings) is gratefully acknowledged.

References (30)

  • H. Braak et al.

    Neuropathological stageing of Alzheimer-related changes

    Acta Neuropathol.

    (1991)
  • H. Braak et al.

    Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections

    Brain Pathol.

    (1991)
  • H. Braak et al.

    Pathology of Alzheimer’s disease

  • H. Braak et al.

    Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis

    Acta Neuropathol.

    (1996)
  • H. Braak et al.

    Silver impregnation of Alzheimer’s neurofibrillary changes counterstained for basophilic material and lipofuscin pigment

    Stain Technol.

    (1988)
  • Cited by (1412)

    View all citing articles on Scopus
    View full text