Intended for healthcare professionals

Clinical Review

Science, medicine, and the future: Alzheimer's disease

BMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7129.446 (Published 07 February 1998) Cite this as: BMJ 1998;316:446
  1. Colin L Masters, head (c.masters@pathology.unimelb.edu.au)a,
  2. Konrad Beyreuther, directorb
  1. a Department of Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia
  2. b Center for Molecular Biology, University of Heidelberg, D-69120 Heidelberg, Germany
  1. Correspondence to: Professor Masters

    Introduction

    There is a noticeable air of optimism in the research community studying Alzheimer's disease. This because the molecular basis of Alzheimer's disease and other neurodegenerative conditions, such as Parkinson's and Huntington's diseases, is rapidly being elucidated. From these molecular insights, it is likely that effective therapeutic strategies will be developed within the next 10 years. Future treatment will probably be based on combination therapies—such as neurotransmitter replacement combined with a drug to protect against the toxic effect of Aß amyloid—tailored to the genetic profile of an individual. Assuming proved efficacy and safety, these forms of treatment are likely to be as widespread and acceptable as cholesterol lowering treatment is today.

    In the past few years there has been an avalanche of knowledge surrounding the genesis of Aß amyloid plaques, one of the principal pathological hallmarks of this disease (see fig 1). In the absence of a serious candidate for the pathway leading to the neurofibrillary tangle, the other major pathological lesion in Alzheimer's disease (fig 1), the focus will probably remain on amyloid plaques. Strong genetic risk factors have been identified for Alzheimer's disease, all of which interact directly or indirectly with the Aß amyloid pathway. Undoubtedly, other genetic factors remain to be discovered, some of which might open the door to the neurofibrillary tangle. More importantly, the major environmental risk factors for Alzheimer's disease remain elusive. This is not surprising, given the relatively few analytical epidemiological studies that have been conducted and the difficulty of case ascertainment, particularly in the early stages of the disease.

    Fig 1

    The central pathway leading to Alzheimer's disease involves the processing of amyloid precursor protein into Aß amyloid, which accumulates as amyloid plaques or perivascular amyloid. Concomitantly, degeneration occurs in neurons and their processes, leading to neurofibrillary tangles. (Images are from Spielmeyer's Histopathology of the …

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