EXAMINATION OF THE VALIDITY OF THE HIERARCHICAL MODEL OF NEUROPATHOLOGICAL STAGING IN NORMAL AGING AND ALZHEIMERS-DISEASE

The neuropathological staging model of Alzheimer's disease proposed by Braak and Braak [Acta Neuropathol (1991) 82:259] requires that the ev olution of neurofibrillary pathology follows a predictable pattern tha t can be ordered in a regular regional hierarchy.We have operationaliz ed the neuropathological staging system re, permit testing of its: val idity. Forty-two cases were derived from an epidemiological study or c ognitive function in an elderly population for which post-mortem brain tissue was collected. Cases with neuropathological diagnoses other th an Alzheimer's disease and normal aging were excluded. Neurofibrillary tangle counts were determined in all cortical laminae anti regions us ed for staging. There was a significant correlation between the overal l extent of neurofibrillary pathology and the number of regions affect ed. There were frequent order violations in the a proposed hierarchy: 19 instances (45%) involving entorhinal and transentorhinal cortices, and 16 instances (38%) involving CAI of hippocampus and entorhinal cor tex, Only 6 out of 42 cases conformed in all regions to the expected h ierarchy. Nevertheless. 90% of the cases had 2 order violations or les s, supporting the approximate validity of the hierarchy.