Neuropathological criteria for the diagnosis of Alzheimer's disease: are we really ready yet?

Neurobiol Aging. Jul-Aug 1997;18(4 Suppl):S3-12. doi: 10.1016/s0197-4580(97)00074-2.


The specific diagnosis of AD as a particular dementia from which a patient suffered assumes, debatably, a reasonably pure clinicopathological entity in which the same concatenation of lesions will not be encountered in others dying with a similar clinical disorder. Statistically complex computations such as multivariate analyses of morphometric data from our laboratory and similar attempts in Swedish and British series may not prove pragmatic for pathological confirmation. The Braaks' schema posits six stages in the evolution of AD. Unfortunately, application of this model to 50 British autopsies cannot reliably identify those cases clinically diagnosed as demented. Furthermore, lack of universal definition for each of the probable lesional subtypes augments the difficulty devising a quantitative consensus. Disease stage refers to a progressive increase in anatomical (geographic) extent of involvement, whereas, grade refers to a progressive increase in severity of affliction within any one site. There is only a tendency for stage and grade to progress in parallel. Nor is it obligatory that either always does progress. More energies should be concentrated upon determining which histopathological abnormality is most injurious to neuronal integrity. Dutch workers opine that in both normal aging and AD, claims of massive, neocortical nerve cell loss may have been based on inadequate morphometry and/or a loss of markers. Requiring urgent resolution is whether cellular changes seen in brains of aging normals represent merely the earliest phase of typical AD (and therefore a good model for Alzheimer pathogenesis), or rather reflect a totally different aging syndrome distinct from AD. We have proposed that abnormalities in the hippocampal formation (with or without neocortical neuronal lesions) may underlie a decline of all higher cognitive functions in senile dementia Alzheimer type. West and colleagues optical disector approach likewise shows that neurodegeneration associated within aging individuals' hippocampi is quantitatively and qualitatively distinct from the neuronal loss in AD. Clinical confreres' imprecision whether or when to term subtle cognitive loss "incipient AD" is understandably mirrored by residual neuropathological struggles to dichotomize such brains as "normative aging" distinct from "putative AD."

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology*
  • Brain / pathology*
  • Cell Count
  • Diagnosis, Computer-Assisted
  • Diagnosis, Differential
  • Disease Progression
  • Hippocampus / pathology
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Severity of Illness Index
  • Terminology as Topic