Simplified Braak and Braak Staging Scheme of Chu et al for Alzheimer-Related Neurofibrillary Changes

 

According to Braak and Braak:

(1) The distribution pattern and packing density of amyloid deposits are not useful for staging.

(2) The distribution of neuritic plaques varies widely.

(3) The distribution of neurofibrillary tangles and neuropil threads exhibit a characteristic distribution pattern that can be used for staging patients with Alzheimer disease..

 

Examination: histology of sections from human brain taken at specified sites

 

Staining: immunohistochemistry with antibodies to ubiquitin (which detects the ubiquitin deposited in the neurofibrillary tangles). The Braak and Braak studies were done with silver stains.

Section According to Braak and Braak (Figure 14, page 257)	Section According to Chu et al (Figure 1, page 422)
uncus (entorhinal and transentorhinal regions)	transentorhinal
lateral geniculate body (hippocampus)	limbic (temporal lobe)
occipital pole (striate area, parastriate field, peristriate region)	neocortical (primary visual cortex)

 

In the original staging system of Braak and Braak, neurofibrillary tangles in Stage I are few and limited to a few areas (entorhinal, transentorhinal, antero-dorsal nucleus of thalamus) while in Stage VI there are a some everywhere with large numbers in some places. The stages in-between represent increasing numbers in more locations.

 

Basic patterns of Braak and Braak:

(1) transentorhinal stages I and II: involvement primarily limited to the transentorhinal layer pre-alpha

(2) limbic stages III and IV: marked involvement of layer pre-alpha in both transentorhinal region and proper entorhinal cortex plus mild involvement of first Ammon's horn

(3) isocortical stages V and VI: destruction of virtually all isocortical association areas

 

Location (Chu et al)	Number of Neurofibrillary Tangles	Stage
transentorhinal	modest	I
transentorhinal	numerous	II
limbic	modest	III
limbic	numerous	IV
neocortical	modest	V
neocortical	numerous	VI