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Background: Pathologic changes in the Alzheimer disease (AD) brain occur in a hierarchical neuroanatomical pattern affecting cortical, subcortical, and limbic regions.

Objective: To define the time course of pathologic and biochemical changes-amyloid deposition, amyloid [beta]-peptide (A[beta]) accumulation, neurofibrillary tangle (NFT) formation, synaptic loss, and gliosis-within the temporal association cortex of AD cases of varying disease duration, relative to control brains.

Methods: Stereologic assessments of amyloid burden and tangle density as well as ELISA-based measurements of A[beta], synaptophysin, and glial fibrillary acidic protein (GFAP) were performed in the superior temporal sulcus from a cohort of 83 AD and 26 nondemented control brains.

Results: Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid-extractable A[beta] species, reduced levels of synaptophysin, and elevated levels of GFAP. In AD cases, the duration of dementia correlated with the degree of tangle formation, gliosis, and synaptic loss but not with any A[beta] measures. Accumulation of A[beta], measured both neuropathologically and biochemically, was markedly increased in AD brains independent of disease duration, even in cases of short duration.

Conclusions: These data support distinct processes in the initiation and progression of AD pathology within the temporal cortex: Deposition of A[beta] reaches a "ceiling" early in the disease process, whereas NFT formation, synaptic loss, and gliosis continue throughout the course of the illness.

(C) 2004 American Academy of Neurology