The neuropathology of Alzheimer's disease: a review with pathogenetic, aetiological and therapeutic considerations

The neuropathology of Alzheimer's disease is reviewed in this paper emphasizing the morphological and morphometric changes that occur in the disease and their relationship to age and ageing. From this, a new hypothesis of pathogenesis is presented which accounts for the pattern of neuronal damage in Alzheimer's disease. This is that the pathogenesis of Alzheimer's disease begins with a leakage of a neurotoxin through a defective cortical blood brain barrier. This incites development of the senile plaque and later, via a retrograde transport of the same (or different) factors, intracellular neurofibrillary tangle formation and death of neurones within areas of cortex affected by plaques and in subcortical areas such as nucleus basalis of Meynert, locus caeruleus and dorsal raphe nuclei, all of which project to these same areas of cortex. Evidence consistent with this hypothesis is presented and the aetiological and therapeutic implications are discussed.