Contents

Search

Braak staging of Alzheimer's disease

Braak & Braak define 2 separate staging criteria for neuropathologic staging of Alzheimer's disease. Staging: === staging based on PHF-tau pathology === Braak 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 confined to transentorhinal layer pre-alpha - limbic stages 3-4: incipient AD - involvement of CA1 - neocortical stages 5-6: fully developed AD - involvement of all areas of association cortex * microglial activation & PHF-tau propagate jointly across Braak stages [2] === staging based on beta-amyloid pathology === 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 - stage 1: - low densities of amyloid in the neocortex, especially the basal part of frontal lobe, temporal lobe & occipital lobe - 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 - stage 2: - medium densities of amyloid deposits are present in all areas of association cortex - only the primary sensory cortex & 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 layer 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 - stage 3: - virtually all areas of the cortex are involved including primary sensory cortex & 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

General

histopathology of Alzheimer's disease staging of Alzheimer's disease

References

  1. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82(4):239-59. Review. PMID: 1759558
  2. Pascoal TA, Benedet AL, Ashton NJ et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med 2021. August 21 PMID: 34446931 https://www.nature.com/articles/s41591-021-01456-w

Slides & Images

NFT & neuropil thread by stage & region (Braak & Braak) image related to Braak staging of Alzheimer's disease