The neuropathology of Alzheimer's disease in the year 2005

doi:10.1017/CBO9780511544873.030

29 - The neuropathology of Alzheimer's disease in the year 2005

from Part IV - Alzheimer's disease

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

Colin L. Masters and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Colin L. Masters: Affiliation:
Department of Pathology, University of Melbourne and the Mental Health Research Institute of Victoria, Parkville, Australia
Konrad Beyreuther: Affiliation:
Centre for Molecular Biology, University of Heidelberg, Heidelberg, Germany

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Summary

Introduction

The current molecular era of the neuropathology of Alzheimer's disease began in the early 1970s with the first attempts to characterize the biochemical basis of the amyloid deposits (now designated Aβ), which remain the pathognomic feature of this illness (Nikaido et al., 1971). Subsequent dramatic progress in amino acid sequencing (Glenner & Wong, 1984; Masters et al., 1985), gene cloning (Kang et al., 1987), and elucidation of the biogenesis of the Aβ amyloid protein (for recent reviews see Beyreuther et al., 2001; Cummings & Cole, 2002; Hardy & Selkoe, 2002; Ines Dominguez & DeStrooper, 2002; McLean et al., 2001; Sisodia & St George-Hyslop, 2002) have led to a coherent picture of the pathogenesis of AD. However, this explosion of knowledge on AD still has not been fully translated back into the clinic, the pathology laboratory, or the mortuary, where diagnostic criteria remain subjective and ambiguous. As the natural history of AD becomes better understood at the molecular level, it would be highly desirable to develop standardized protocols for diagnosis based around the principal biochemical pathway: the biogenesis and accumulation of Aβ amyloid in susceptible areas of the brain (Fig. 29.1). This chapter outlines the traditional methods of neuropathologic diagnosis, together with some approaches to the contemporary molecular diagnosis of AD both during life and after death (Fig. 29.2), which should have general applicability to the other major diseases caused by the toxic gains-of-function of α-synuclein (Parkinson's disease; diffuse Lewy body disease; multiple system atrophy), prion protein (Creutzfeldt–Jakob and related diseases); Cu–Zu superoxide dismutase (amyotrophic lateral sclerosis); polyglutamine expansions (Huntington's disease and mechanistically related illnesses) and the tau microtubule associated protein (frontotemporal degenerations; Pick's disease; cortico-basal degeneration; progressive supranuclear palsy).

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 433 - 440

DOI: https://doi.org/10.1017/CBO9780511544873.030 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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