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- Braak & Braak define 2 separate staging criteria for neuropathologic staging of Alzheimer's disease.
- Staging of Alzheimer's disease based upon histopathology of neurofibrillary tangles & neuropil threads in autopsy specimens. The distribution & packing density of amyloid plaques varies widely & is of little significance for differentiation of neuropathologic stages.
- 6 stages distinguished by location & severity of changes see 'NFT & neuropil thread by stage & region (Braak & Braak)'
- trans- entorhinal stages 1-2: clinically silent
- involvement of CA1
- neocortical stages 5-6: fully developed AD
- involvement of all areas of association cortex
- Most amyloid plaques are not associated with neurofibrillary changes & neurons within the amyloid appear normal. In early stages of Alzheimer's disease, amyloid plaques show considerable variability in shape, size & quantity. End-stage Alzheimer's disease shows a fairly consistent distribution pattern of amyloid plaques.
- 3 stages of amyloid deposition are described
- Low densities of amyloid in the neocortex, especially the basal part of frontal, temporal & occipital lobes. The hippocampus is free of amyloid. The parvocellular layer of the presubiculum & the entorhinal cortex layers pre-beta & pre-gamma show weakly- staining bands of amyloid.
- Medium densities of amyloid deposits are present in all areas of association cortex. Only the primary sensory & primary motor cortex remain free of amyloid. All layers of the cortex are are are affected; only the external glial layer remains free of amyloid. Regions of white matter underlying the cortex show small, condensed deposits of amyloid. The hippocampus has limited amyloid deposition. A few globular deposits of amyloid are restricted to the pyramidal layers of the CA1 & subiculum. Additionally, densely packed rows of amyloid occur in the molecular layer of the subiculum extending into the stratum radiatum of CA1 & the molecular layr of the dentate gyrus The parvocellular layer of the presubiculum is filled with diffusely distributed amyloid. Bands of amyloid may be seen in the entorhinal cortex.
- Virtually all areas of the cortex are involved including primary sensory & primary motor cortex. The hippocampus shows relatively few deposits. Gradual involvement of subcortical regions occurs. The striatum, thalamus, hypothalamus, subthalamus & red nucleus show deposits. The molecular layer of the cerebellum may contain patches of amyloid. The substantia nigra remains free of amyloid.
More General Terms
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82(4):239-59. Review. PMID: 
Braak staging of Alzheimer's disease