In Search of Possible Markers and Models in Alzheimer’s Disease

Abstract

The search for therapeutic agents effective in Alzheimer’s disease is hampered by two major problems. First, there is no specific animal model which reproduces the biochemical, morphological and behavioural characteristics of the disease. Thus drug screening tends to be based on the search for a biochemical activity considered to be necessary in the therapy of Alzheimer’s disease. This is the case in the search for cholinomimetic agents as a replacement therapy for the defective cholinergic innervation in the cortex and hippocampus. The extrapolation from screening to clinical testing in these cases is, however, extremely uncertain. The second difficulty is that of diagnosis. Since Alzheimer’s disease is a progressive, degenerative disease, any therapy would be expected to be most effective in the early stages when the deficiency is less marked and the cause possibly still reversible. Unfortunately, at this very early stage the symptoms of Alzheimer’s disease are easily confused with those of various other psychiatric and neurological diseases such as depression and Parkinsonism, and even iatrogenic conditions such as subacute benzodiazepine toxicity.